Radiation Protection

**Chapter 1**

**Abstract**

Relative Biological Effectiveness

from Folded Tandem Ion

*Rajesh Chaurasia, Kapil Shirsath, Utkarsha Desai,*

*S.K. Gupta, B.K. Sapra and Narayana Yerol*

Theoretical Approach

is not possible using conventional methods.

cell survival and gene conversion

**1. Introduction**

**3**

Studies Using 3 MeV Proton Beam

Accelerator: An Experimental and

*Rajesha K. Nairy, Nagesh N. Bhat, K.B. Anjaria, Usha Yadav,*

Proton being the easiest light ion to accelerate and achieve desired beam profile, has been pursued as a popular particulate radiation for therapy applications. In the present study, *Saccharomyces cerevisiae* D7 strain was used to estimate the RBE values of the 3 MeV proton beam, and an attempt was made to derive mathematical formula for calculating RBE value with respect to the dose. Dosimetry studies were carried out using Fricke dosimetry and Semiconductor Surface Barrier detector to calibrate the absorbed doses of Gamma chamber-1200 and Folded Tandem Ion Accelerator respectively. Gold standard cell survival assay and gene conversion assay were used to compare gamma and proton radiation induced cell death and genetic endpoint. Multi target single hit model was used to derive mathematical formula for RBE estimation. The results show a linear survival-dose response after proton radiation and sigmoid survival-dose response after gamma radiation treatment. The calculated RBE value from the survival and gene conversion studies was 1.60 and 3.93, respectively. The derived mathematical formula is very useful in calculating RBE value, which varies from 3.61 to 1.80 with increasing dose. The estimated RBE value from the mathematical formula is comparable with the experimental values. With the help of the present mathematical formulation, RBE value at any dose can be calculated in the exponential and sigmoidal regions of the survival curve without actually extending the experiment in that dose region, which

**Keywords:** *Saccharomyces cerevisiae*, relative biological effectiveness, radiation dose,

Biological effects of heavy charged particles on humans play an important role in two different scientific fields; in radiation therapy using protons and heavier ions

#### **Chapter 1**

## Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem Ion Accelerator: An Experimental and Theoretical Approach

*Rajesha K. Nairy, Nagesh N. Bhat, K.B. Anjaria, Usha Yadav, Rajesh Chaurasia, Kapil Shirsath, Utkarsha Desai, S.K. Gupta, B.K. Sapra and Narayana Yerol*

#### **Abstract**

Proton being the easiest light ion to accelerate and achieve desired beam profile, has been pursued as a popular particulate radiation for therapy applications. In the present study, *Saccharomyces cerevisiae* D7 strain was used to estimate the RBE values of the 3 MeV proton beam, and an attempt was made to derive mathematical formula for calculating RBE value with respect to the dose. Dosimetry studies were carried out using Fricke dosimetry and Semiconductor Surface Barrier detector to calibrate the absorbed doses of Gamma chamber-1200 and Folded Tandem Ion Accelerator respectively. Gold standard cell survival assay and gene conversion assay were used to compare gamma and proton radiation induced cell death and genetic endpoint. Multi target single hit model was used to derive mathematical formula for RBE estimation. The results show a linear survival-dose response after proton radiation and sigmoid survival-dose response after gamma radiation treatment. The calculated RBE value from the survival and gene conversion studies was 1.60 and 3.93, respectively. The derived mathematical formula is very useful in calculating RBE value, which varies from 3.61 to 1.80 with increasing dose. The estimated RBE value from the mathematical formula is comparable with the experimental values. With the help of the present mathematical formulation, RBE value at any dose can be calculated in the exponential and sigmoidal regions of the survival curve without actually extending the experiment in that dose region, which is not possible using conventional methods.

**Keywords:** *Saccharomyces cerevisiae*, relative biological effectiveness, radiation dose, cell survival and gene conversion

#### **1. Introduction**

Biological effects of heavy charged particles on humans play an important role in two different scientific fields; in radiation therapy using protons and heavier ions

and in space research for understanding effects on space travelers from galactic cosmic radiation [1]. In addition, the low energy heavy ion accelerators have an important role in basic and applied sciences [2]. Proton being the easiest light ion to accelerate and achieve desired beam profile, has been pursued as a popular particulate radiation for therapeutic applications. Nonetheless, very less has been understood about biological effectiveness of these charged particles. Proton beams can provide highly localized, uniform doses of radiation to tumors, while sparing the surrounding normal tissues, compared with conventional modalities using photons or electrons [3]. In addition to therapeutic applications, energetic proton also finds its presence in space research, neutron dosimetry wherein due to elastic scattering of energetic neutrons lead to (n, p) reaction and creation of low energy protons in the tissues.

detectors, one mounted inside scattering chamber (Monitor detector) and other on sample position (Sample detector). Position of the beam was visualized using a quartz crystal mounted on a movable ladder in a general purpose scattering chamber maintained in ultra-high vacuum. The pencil beam was made to channel through blank position on the ladder and passed through drift tube of length of about 3 meters. The primary beam was then made to pass through titanium window at the end of drift tube. The beam position was again visualized by keeping a quartz plate after the window. The position of beam was adjusted to the center of the window using X-Y steerer magnets and focused using a quadrupole magnet. Once the beam was tuned to desired geometry and position, the ladder in the scattering chamber was moved so that beam passed through a gold foil of 500 ng/cm<sup>2</sup> thickness. The diffused beam facilitated uniform beam profile at the titanium window. An SSB detector inside the scattering chamber kept at an angle from gold foil helped to monitor the fluence. Another SSB detector was positioned at the position where samples could be mounted, simulating the geometry of sample. The detector was provided with a calibrated collimator to reduce count rate and the fluence measurement was normalized between the two detectors. The profile of the beam was measured by scanning the entire area of titanium window. Intensity of beam was adjusted by varying ion source current. LET measurements were done using TRIM software. The position of the monitor detector was adjusted in such a way that the count rate and dead time of the detector are acceptable. Initial signals from the detector were amplified and digitalized using Multi Channel Analyzer (MCA). The number of scattered proton particles (Monitor proton counts) and diffused proton particles (Sample proton counts) were counted for 100 sec with multiple trials to get the ratio. The fluence of the proton beam at source detector was calculated to

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem…*

*DOI: http://dx.doi.org/10.5772/intechopen.94243*

Absorbed dose was calculated using the relation [Kraft et al. 1989]

be 13 KeV/μm. The fluence of the source detector was measured using

ratio <sup>¼</sup> *NM NS*

Substituting Eqs. (3) and (2) in (1) gives

Rearranging Eq. (4), gives

**5**

Fluence Fð Þ Source Detector <sup>¼</sup> ½ � No*:*of particles on source detector

Dose <sup>¼</sup> <sup>1</sup>*:*<sup>6</sup> � <sup>10</sup>�<sup>8</sup> � � � *LET eVÅ*�<sup>1</sup> � � � *<sup>ϕ</sup>* particles cm‐<sup>2</sup> � � h i (1)

*π* � *rS*

*<sup>π</sup>* � *rS* ð Þ <sup>2</sup> � ratio � � (4)

<sup>1</sup>*:*<sup>6</sup> � <sup>10</sup>�<sup>8</sup> � � � <sup>13</sup> " # (5)

<sup>2</sup> � ratio

<sup>2</sup> ð Þ (2)

ratio (3)

Where fluence represents particles delivered per unit area and LET represents energy transferred per unit length. The LET of the present setup was estimated to

Where 'rs' represents, sample detector collimator radius. Number of particles on sample detector can be calculated by taking ratio between monitor detector and

Dose <sup>¼</sup> <sup>1</sup>*:*<sup>6</sup> � <sup>10</sup>�<sup>8</sup> � � � <sup>13</sup> � *NM*

<sup>N</sup>*<sup>M</sup>* <sup>¼</sup> *Dose* � *<sup>π</sup>* � *rS*

<sup>⇔</sup> *NS* <sup>¼</sup> *NM*

measure absorbed dose.

source detector counts

The radiobiological studies conforms that equal physical doses of different types of radiation do not produce equal biological effects, because of differences in their energy deposition patterns. This is taken into account by the concept of Relative Biological Effectiveness (RBE). RBE compares the severity of damage induced by a radiation under test, at a dose DT relative to the reference radiation dose DR for producing same biological effect. The reference radiation is commonly 60Co-gamma radiation. Generally, the RBE depends on many factors such as the radiation dose, linear energy transfer (LET) at a given tissue depth, dose rate, energy of the radiation, test system and studied biological endpoint. The RBE values of the radiation are very useful in risk estimation during accidental exposure of ionizing radiation (IR) [4]. Revisions in weighting factors for intermediate and very high energy neutrons as well as accelerated protons in the recent ICRP recommendation has drawn more attention to mechanistic approach of studies using radiobiological endpoints.

In the present study, *Saccharomyces cerevisiae* D7 strain was used to study biological effects of 3 MeV proton radiation using cell survival and gene conversion endpoints. The results obtained were compared with standard 60Co gamma radiation. An attempt has been made to estimate RBE value for 3 MeV proton radiation and variation of RBE value as a function of dose with experimental and theoretical formulations. The model organism considered in the study is Saccharomcyces cerevisiae (budding yeast), which is a useful model for higher eukaryotic organisms study and plays a vital role in modern day research. The conservation of many processes such as replication, DNA damage, replication checkpoints and cell cycle control is observed in Saccharomcyces cerevisiae [5]. Additionally, it has been shown that 42% of yeast genes that cause chromosome instability are conserved in humans, demonstrating the importance of yeast in the study of genomic instability and cancer [6]. The prevalence of budding yeast in research today can also be attributed to the low cost at which, experimental procedures can be completed, coupled with its relatively quick doubling time [7].

#### **2. Materials and methods**

**Gamma source and Dosimetry:** 60Co-gamma chamber-1200 supplied by the Isotope Division, Bhabha Atomic Research Center was used for irradiating the cell samples. Fricke dosimetry system was used to calibrate the gamma chamber; the details were given elsewhere [8–15].

**Proton Beam Source and Dosimetry:** Proton beams are accelerated using the Folded Tandem Ion Accelerator (FOTIA), a facility at Bhabha Atomic Research Centre (BARC), is an electrostatic accelerator with a maximum terminal voltage of 6 MV [2]. Dosimetry of FOTIA was carried out using 2 Silicon Surface Barrier (SSB) *Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem… DOI: http://dx.doi.org/10.5772/intechopen.94243*

detectors, one mounted inside scattering chamber (Monitor detector) and other on sample position (Sample detector). Position of the beam was visualized using a quartz crystal mounted on a movable ladder in a general purpose scattering chamber maintained in ultra-high vacuum. The pencil beam was made to channel through blank position on the ladder and passed through drift tube of length of about 3 meters. The primary beam was then made to pass through titanium window at the end of drift tube. The beam position was again visualized by keeping a quartz plate after the window. The position of beam was adjusted to the center of the window using X-Y steerer magnets and focused using a quadrupole magnet. Once the beam was tuned to desired geometry and position, the ladder in the scattering chamber was moved so that beam passed through a gold foil of 500 ng/cm<sup>2</sup> thickness. The diffused beam facilitated uniform beam profile at the titanium window. An SSB detector inside the scattering chamber kept at an angle from gold foil helped to monitor the fluence. Another SSB detector was positioned at the position where samples could be mounted, simulating the geometry of sample. The detector was provided with a calibrated collimator to reduce count rate and the fluence measurement was normalized between the two detectors. The profile of the beam was measured by scanning the entire area of titanium window. Intensity of beam was adjusted by varying ion source current. LET measurements were done using TRIM software. The position of the monitor detector was adjusted in such a way that the count rate and dead time of the detector are acceptable. Initial signals from the detector were amplified and digitalized using Multi Channel Analyzer (MCA). The number of scattered proton particles (Monitor proton counts) and diffused proton particles (Sample proton counts) were counted for 100 sec with multiple trials to get the ratio. The fluence of the proton beam at source detector was calculated to measure absorbed dose.

Absorbed dose was calculated using the relation [Kraft et al. 1989]

$$\text{Dose} = \left[ \left( \mathbf{1.6} \times \mathbf{10}^{-8} \right) \times \text{LET} \left( \text{eV} \, \text{Å}^{-1} \right) \times \phi \left( \text{particles cm}^{-2} \right) \right] \tag{1}$$

Where fluence represents particles delivered per unit area and LET represents energy transferred per unit length. The LET of the present setup was estimated to be 13 KeV/μm. The fluence of the source detector was measured using

$$\text{Fluence (F) Source Detector} = \frac{[\text{No.of particles on source detector}]}{(\pi \times r\_S^2)} \qquad \text{(2)}$$

Where 'rs' represents, sample detector collimator radius. Number of particles on sample detector can be calculated by taking ratio between monitor detector and source detector counts

$$\text{ratio} = \frac{N\_M}{N\_S} \Leftrightarrow N\_S = \frac{N\_M}{\text{ratio}} \tag{3}$$

Substituting Eqs. (3) and (2) in (1) gives

$$\text{Dose} = \left[ \frac{\left( \mathbf{1.6} \times \mathbf{10}^{-8} \right) \times \mathbf{13} \times \mathbf{N\_M}}{\left( \pi \times r\_S^2 \times \text{ratio} \right)} \right] \tag{4}$$

Rearranging Eq. (4), gives

$$\mathbf{N}\_M = \left[ \frac{Dose \times \pi \times r\_S^2 \times \text{ratio}}{\left(1.6 \times 10^{-8}\right) \times 13} \right] \tag{5}$$

and in space research for understanding effects on space travelers from galactic cosmic radiation [1]. In addition, the low energy heavy ion accelerators have an important role in basic and applied sciences [2]. Proton being the easiest light ion to accelerate and achieve desired beam profile, has been pursued as a popular particulate radiation for therapeutic applications. Nonetheless, very less has been understood about biological effectiveness of these charged particles. Proton beams can provide highly localized, uniform doses of radiation to tumors, while sparing the surrounding normal tissues, compared with conventional modalities using photons or electrons [3]. In addition to therapeutic applications, energetic proton also finds its presence in space research, neutron dosimetry wherein due to elastic scattering of energetic neutrons lead to (n, p) reaction and creation of low energy protons in

*Recent Techniques and Applications in Ionizing Radiation Research*

The radiobiological studies conforms that equal physical doses of different types of radiation do not produce equal biological effects, because of differences in their energy deposition patterns. This is taken into account by the concept of Relative Biological Effectiveness (RBE). RBE compares the severity of damage induced by a radiation under test, at a dose DT relative to the reference radiation dose DR for producing same biological effect. The reference radiation is commonly 60Co-gamma radiation. Generally, the RBE depends on many factors such as the radiation dose, linear energy transfer (LET) at a given tissue depth, dose rate, energy of the radiation, test system and studied biological endpoint. The RBE values of the radiation are very useful in risk estimation during accidental exposure of ionizing radiation (IR) [4]. Revisions in weighting factors for intermediate and very high energy neutrons as well as accelerated protons in the recent ICRP recommendation has drawn more attention to mechanistic approach of studies using radiobiological

In the present study, *Saccharomyces cerevisiae* D7 strain was used to study biological effects of 3 MeV proton radiation using cell survival and gene conversion endpoints. The results obtained were compared with standard 60Co gamma radiation. An attempt has been made to estimate RBE value for 3 MeV proton radiation and variation of RBE value as a function of dose with experimental and theoretical formulations. The model organism considered in the study is Saccharomcyces cerevisiae (budding yeast), which is a useful model for higher eukaryotic organisms study and plays a vital role in modern day research. The conservation of many processes such as replication, DNA damage, replication checkpoints and cell cycle control is observed in Saccharomcyces cerevisiae [5]. Additionally, it has been shown that 42% of yeast genes that cause chromosome instability are conserved in humans, demonstrating the importance of yeast in the study of genomic instability and cancer [6]. The prevalence of budding yeast in research today can also be attributed to the low cost at which, experimental procedures can be completed,

**Gamma source and Dosimetry:** 60Co-gamma chamber-1200 supplied by the Isotope Division, Bhabha Atomic Research Center was used for irradiating the cell samples. Fricke dosimetry system was used to calibrate the gamma chamber; the

**Proton Beam Source and Dosimetry:** Proton beams are accelerated using the Folded Tandem Ion Accelerator (FOTIA), a facility at Bhabha Atomic Research Centre (BARC), is an electrostatic accelerator with a maximum terminal voltage of 6 MV [2]. Dosimetry of FOTIA was carried out using 2 Silicon Surface Barrier (SSB)

coupled with its relatively quick doubling time [7].

**2. Materials and methods**

**4**

details were given elsewhere [8–15].

the tissues.

endpoints.

Eq. (5) was used to calculate required number of monitor detector counts for desired absorbed dose.

**Sample preparation and irradiation:** A mutant type diploid yeast strain, *Saccharomyces cerevisiae* D7 was used for the study. The genotype of the strain is

$$\frac{a}{\infty} \frac{ade2-40}{ade2-119}, \frac{trp5-12}{trp5-27}, \frac{ilv1-92}{ilv1-92}$$

The single cell stationary-phase cultures were obtained by growing the cells Yeast extract: Peptone: Dextrose (YEPD) (1%:2%:2%) medium for several generations to a density of approximately 3 <sup>10</sup><sup>8</sup> cells mL<sup>1</sup> . Cells were washed thrice by centrifugation (2000 g for 5 min) and re-suspended to a cell concentration of <sup>1</sup> <sup>10</sup><sup>8</sup> cells mL<sup>1</sup> (by counting in heamocytometer) in sterile double distilled water. For proton radiation, the cell suspension was mixed well and exactly 1 108 cells were filtered using millipore filter assembly in aseptic condition. The filter paper having cells on the surface was placed inside sterile 3 cm diameter petri dish and irradiated for different doses. For gamma ray irradiation, polypropylene vials were used containing 1 <sup>10</sup><sup>8</sup> cells per ml. Cell suspensions were maintained at 0–4° C before and after irradiation till plating.

**Survival assay and Gene conversion assay:** Treated and untreated samples were suitably diluted and plated in quadruplicate on YEPD agar medium. Plates were incubated for 2–3 days at 30°C in the dark, and the colonies were counted. The gene conversion assay was conducted by plating 1 <sup>10</sup><sup>6</sup> cells per plate on Trpagar medium and incubated for 72 h at 30°C in the dark, and the colonies were counted.

#### **3. Results and discussion**

**Calibration of 60Co-1200 Source:** In the present study, vials containing Fricke dosimetry solution were exposed to gamma rays for different time interval. Optical absorbance measurements of the dosimeter were done at 304 nm wavelength using a UV–Visible spectrophotometer. The absorbed dose was calculated using optical absorbance and is presented in **Figure 1**. Dose response was considered to be best fit with linear model, with a regression coefficient equal to 0.99. The dose rate of the gamma chamber was determined by the same method and was found to be 51 Gy min<sup>1</sup> . The dose calibrations are traceable to the National standards.

**Calibration of FOTIA:** The beam profile of the FOTIA was measured using a collimated SSB detector. The dosimetry methods followed is presented in materials and methods section, uniformity of the beam at sample position was measured by placing sample detector vertically and horizontally at different positions from the central axis.

**Cell Inactivation Studies:** The survival response of *Saccharomyces cerevisiae* D7 strain after irradiation with proton and gamma radiation is presented in **Figure 2**. It is clear from **Figure 3** that dose response with proton beam is linear, whereas with gamma radiation it is sigmoid. The sigmoid dose response is due to the multi-track hit processes combined with dose rate dependent molecular repair processes [9–11]. The linear dose–response is due to the lethal damage which leads to cell death even at lower doses. The absence of shoulder indicates absence of sub lethal damage repair in the case of proton radiation, whereas for gamma radiation, the shoulder indicates that most of the induced sublethal damages were easily repaired at lower doses.

SGamma = (1-(1-exp(0.00459 D))3.78) (with R2 = 0.99 and Chi2 = 0.00012) and SProton = (1-(1-exp(0.00736 D))1.50) (with R2 = 0.99 and Chi<sup>2</sup> = 0.00056). The calculated D0 value, which is a reciprocal of the inactivation constant, is 218 and 136 Gy for gamma and proton radiation respectively. The RBE value in the exponential region can be calculated by taking ratio between inactivation constant of

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem…*

*Dose–response relation after irradiation with proton (*●*) and gamma radiation (*■*).*

**Gene conversation studies:** Gene conversion analysis was carried out using *Saccharomyces cerevisiae* D7 yeast cell line at trp locus. Each colony represents a gene

gamma and proton radiation and is found to be 1.60.

**Figure 2.**

**7**

**Figure 1.**

*Dose calibration curve for 60Co gamma Chamber-1200.*

*DOI: http://dx.doi.org/10.5772/intechopen.94243*

The obtained experimental data were fit to multi-target single hit theory and the survival response of gamma and proton radiation were represented as

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem… DOI: http://dx.doi.org/10.5772/intechopen.94243*

**Figure 1.** *Dose calibration curve for 60Co gamma Chamber-1200.*

**Figure 2.** *Dose–response relation after irradiation with proton (*●*) and gamma radiation (*■*).*

SGamma = (1-(1-exp(0.00459 D))3.78) (with R2 = 0.99 and Chi2 = 0.00012) and SProton = (1-(1-exp(0.00736 D))1.50) (with R2 = 0.99 and Chi<sup>2</sup> = 0.00056). The calculated D0 value, which is a reciprocal of the inactivation constant, is 218 and 136 Gy for gamma and proton radiation respectively. The RBE value in the exponential region can be calculated by taking ratio between inactivation constant of gamma and proton radiation and is found to be 1.60.

**Gene conversation studies:** Gene conversion analysis was carried out using *Saccharomyces cerevisiae* D7 yeast cell line at trp locus. Each colony represents a gene

Eq. (5) was used to calculate required number of monitor detector counts for

*trp*5 12 *trp*<sup>5</sup> <sup>27</sup> ,

The single cell stationary-phase cultures were obtained by growing the cells Yeast extract: Peptone: Dextrose (YEPD) (1%:2%:2%) medium for several genera-

**Survival assay and Gene conversion assay:** Treated and untreated samples were suitably diluted and plated in quadruplicate on YEPD agar medium. Plates were incubated for 2–3 days at 30°C in the dark, and the colonies were counted. The gene conversion assay was conducted by plating 1 <sup>10</sup><sup>6</sup> cells per plate on Trpagar medium and incubated for 72 h at 30°C in the dark, and the colonies were counted.

**Calibration of 60Co-1200 Source:** In the present study, vials containing Fricke dosimetry solution were exposed to gamma rays for different time interval. Optical absorbance measurements of the dosimeter were done at 304 nm wavelength using a UV–Visible spectrophotometer. The absorbed dose was calculated using optical absorbance and is presented in **Figure 1**. Dose response was considered to be best fit with linear model, with a regression coefficient equal to 0.99. The dose rate of the gamma chamber was determined by the same method and was found to be

. The dose calibrations are traceable to the National standards. **Calibration of FOTIA:** The beam profile of the FOTIA was measured using a collimated SSB detector. The dosimetry methods followed is presented in materials and methods section, uniformity of the beam at sample position was measured by placing sample detector vertically and horizontally at different positions from the

**Cell Inactivation Studies:** The survival response of *Saccharomyces cerevisiae* D7 strain after irradiation with proton and gamma radiation is presented in **Figure 2**. It is clear from **Figure 3** that dose response with proton beam is linear, whereas with gamma radiation it is sigmoid. The sigmoid dose response is due to the multi-track hit processes combined with dose rate dependent molecular repair processes [9–11]. The linear dose–response is due to the lethal damage which leads to cell death even at lower doses. The absence of shoulder indicates absence of sub lethal damage repair in the case of proton radiation, whereas for gamma radiation, the shoulder indicates that most of the induced sublethal damages were easily repaired at lower

The obtained experimental data were fit to multi-target single hit theory and

the survival response of gamma and proton radiation were represented as

centrifugation (2000 g for 5 min) and re-suspended to a cell concentration of <sup>1</sup> <sup>10</sup><sup>8</sup> cells mL<sup>1</sup> (by counting in heamocytometer) in sterile double distilled water. For proton radiation, the cell suspension was mixed well and exactly 1 108 cells were filtered using millipore filter assembly in aseptic condition. The filter paper having cells on the surface was placed inside sterile 3 cm diameter petri dish and irradiated for different doses. For gamma ray irradiation, polypropylene vials were used containing 1 <sup>10</sup><sup>8</sup> cells per ml. Cell suspensions were maintained at 0–4°

*ilv*1 92 *ilv*1 92

. Cells were washed thrice by

**Sample preparation and irradiation:** A mutant type diploid yeast strain, *Saccharomyces cerevisiae* D7 was used for the study. The genotype of the strain is

> *a* ∝

*Recent Techniques and Applications in Ionizing Radiation Research*

tions to a density of approximately 3 <sup>10</sup><sup>8</sup> cells mL<sup>1</sup>

C before and after irradiation till plating.

**3. Results and discussion**

51 Gy min<sup>1</sup>

central axis.

doses.

**6**

*ade*2 40 *ade*<sup>2</sup> <sup>119</sup> ,

desired absorbed dose.

Where, DG is gamma radiation dose and DT is test radiation (in this case proton radiation) dose. From multi-target single hit model, the survival can be represented as

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem…*

Where S represents survival fraction, k is inactivation constant, D is dose and n gives number of targets. To calculate RBE value, we are considering same survival

*SG* ¼ *ST*

f g 1 � *nG* exp ð Þ �*kGDG* ¼ f g 1 � *nT* exp ð Þ �*kTDT*

<sup>¼</sup> exp ð Þ �*kTDT* exp ð Þ �*kGDG* � �

¼ exp ð Þ �*kTDT* þ *kGDG*

¼ �ð Þ *kTDT* þ *kGDG*

*kGDG DT*

<sup>¼</sup> ð Þ *kG* � *DG DT*

> þ *kT kG*

� *<sup>σ</sup>nG* ð Þ<sup>2</sup> " #

> � *kT kG* 2

þ

*∂y ∂nT* � �<sup>2</sup>

� *<sup>σ</sup>nT* ð Þ<sup>2</sup>

(10)

(11)

(12)

(13)

� � (9)

� �

� ln *nG nT*

> *∂y ∂nG* � �<sup>2</sup>

> > *nT*

¼ �*kT* þ

� � � �

þ *kT*

ð Þ *DT* � *kG*

Eq. (9) gives the relation between RBE and dose. In Eq. (9), the DT, nT, kT represents dose, number of target and inactivation constant under test radiation condition respectively and nG, kG represents number of target, inactivation constant under gamma radiation condition respectively. The variance in the measurements was calculated using following equations, in Eq. (9) the kG, nG, kT and nT are

> � *<sup>σ</sup>kT* ð Þ<sup>2</sup> " #

þ

" # � �

<sup>¼</sup> <sup>1</sup> *kG* � �<sup>2</sup>

*nG* � *kG* � *DT* � �<sup>2</sup>

<sup>¼</sup> <sup>1</sup>

( )<sup>2</sup>

( " #)

� �

<sup>1</sup> � ½ � <sup>1</sup> � exp ð Þ �*kGDG nG* f g <sup>¼</sup> <sup>1</sup> � ½ � <sup>1</sup> � exp ð Þ �*kTDT nT* f g (8)

level with both the radiations, thus using Eq. (7), we can write

*DOI: http://dx.doi.org/10.5772/intechopen.94243*

Simplifying (8), considering high radiation dose (D)

) *nG nT*

1 *DT*

*RBE* <sup>¼</sup> *DG DT*

variables

**9**

ð Þ *<sup>σ</sup><sup>y</sup>* <sup>2</sup> <sup>¼</sup> *<sup>∂</sup><sup>y</sup>*

*∂kG* � �<sup>2</sup>

� *<sup>σ</sup>kG* ð Þ<sup>2</sup> " #

> *∂y ∂kG* � �<sup>2</sup>

where y represents RBE value

þ

*∂y ∂kT* � �<sup>2</sup>

<sup>¼</sup> �<sup>1</sup> *kG* <sup>2</sup> � *DT* � � � ln *nG*

*∂y ∂nG* � �<sup>2</sup>

*∂y ∂kT* � �<sup>2</sup>

1 *DT* *nG nT*

ln *nG nT* � �

> � ln *nG nT* � �

> > ln *nG nT* � �

� �

<sup>¼</sup> <sup>1</sup>

*<sup>S</sup>* <sup>¼</sup> <sup>1</sup> � ½ � <sup>1</sup> � exp ð Þ �*kD <sup>n</sup>* f g (7)

**Figure 3.** *Gene conversion frequency after irradiating with proton (*●*) and gamma radiation (*■*).*

convertant and data is presented in **Figure 3**. The doses 25 Gy, 75Gy and 100 Gy were selected and the results show a linear increase in gene conversion frequency with dose. In the case of proton radiation, at lower doses increase in gene conversion frequency was linear, whereas at higher doses it attains plateau. In the case of gamma radiation gene conversion frequency was linear throughout the selected dose region. The gene conversion frequency (G.C.F) for gamma and proton radiation were represented as G.C. F.gamma = (6.46 � 2.19) + (6.46 � 0.105) D (with R2 = 0.99) and G.C. F.Proton = (7.02 � 3.44) + (25.44 � 0.520) D (with R2 = 0.99). The RBE value of the proton radiation for gene conversion was calculated using slopes, is 3.93.

**Relative biological effectiveness studies:** In the present study, along with cell inactivation and gene conversion studies, we conducted RBE studies for 3 MeV proton radiations. To estimate RBE value, the experiments were repeated using standard gamma radiation (**Figures 2** and **3**). Estimation of RBE value for proton beam is very important in medical treatment planning, where the RBE values should be known with at least 5–10% accuracy. Generally, a standard RBE value 1.1 is applied to the treatment plan. Recently many authors estimated RBE value for proton beam and they observed that there is a drastic change in RBE value near to Brag's-peak [16–30]. High energy protons have an RBE value of about 1.1, however, for low energy protons still sufficient data is not available to conclude the RBE value. In the present study, we used 3 MeV proton radiation, generally using such energy protons one can observe inside tumor during radiotherapy, so present contributions can be used to strengthen the literature data and can be used to improve proton radiotherapy.

Presently RBE values are calculated on the basis of D0 doses, which give RBE value in the exponential region. In the present study, we formulated an equation, which can be used to calculate RBE value throughout the selected dose-region. Generally RBE is represented by taking the ratio between gamma radiation and test radiation doses, required to produce the same biological effectiveness.

$$\text{RBE} = \frac{D\_G}{D\_T} \text{At same biological effectiveness} \tag{6}$$

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem… DOI: http://dx.doi.org/10.5772/intechopen.94243*

Where, DG is gamma radiation dose and DT is test radiation (in this case proton radiation) dose. From multi-target single hit model, the survival can be represented as

$$\mathcal{S} = \{ \mathbf{1} - [\mathbf{1} - \exp\left(-kD\right)]^n \}\tag{7}$$

Where S represents survival fraction, k is inactivation constant, D is dose and n gives number of targets. To calculate RBE value, we are considering same survival level with both the radiations, thus using Eq. (7), we can write

$$\mathbb{S}\_G = \mathbb{S}\_T$$

$$\{\mathbf{1} - \left[\mathbf{1} - \exp\left(-k\_G D\_G\right)\right]^{\mathfrak{n}\_G}\} = \{\mathbf{1} - \left[\mathbf{1} - \exp\left(-k\_T D\_T\right)\right]^{\mathfrak{n}\_T}\}\tag{8}$$

Simplifying (8), considering high radiation dose (D)

$$\{1 - n\_G \exp\left(-k\_G D\_G\right)\} = \{1 - n\_T \exp\left(-k\_T D\_T\right)\}$$

$$\frac{n\_G}{n\_T} = \left\{\frac{\exp\left(-k\_T D\_T\right)}{\exp\left(-k\_G D\_G\right)}\right\}$$

$$\Rightarrow \frac{n\_G}{n\_T} = \exp\left(-k\_T D\_T + k\_G D\_G\right)$$

$$\ln\left(\frac{n\_G}{n\_T}\right) = \left(-k\_T D\_T + k\_G D\_G\right)$$

$$\frac{1}{D\_T} \times \ln\left(\frac{n\_G}{n\_T}\right) = \left\{-k\_T + \frac{k\_G D\_G}{D\_T}\right\}$$

$$\left\{\left(\frac{1}{D\_T} \ln\left(\frac{n\_G}{n\_T}\right) + k\_T\right) = \frac{(k\_G \times D\_G)}{D\_T}\right\}$$

$$RBE = \frac{D\_G}{D\_T} = \left\{\left[\frac{1}{(D\_T \times k\_G)} \times \ln\left(\frac{n\_G}{n\_T}\right)\right] + \frac{k\_T}{k\_G}\right\}\tag{9}$$

Eq. (9) gives the relation between RBE and dose. In Eq. (9), the DT, nT, kT represents dose, number of target and inactivation constant under test radiation condition respectively and nG, kG represents number of target, inactivation constant under gamma radiation condition respectively. The variance in the measurements was calculated using following equations, in Eq. (9) the kG, nG, kT and nT are variables

$$\left(\left(\sigma\mathfrak{y}\right)^{2} = \left\{ \left[ \left(\frac{\partial\mathfrak{y}}{\partial\mathbf{k}\_{G}}\right)^{2} \times \left(\sigma\_{\mathbf{k}\_{G}}\right)^{2} \right] + \left[ \left(\frac{\partial\mathfrak{y}}{\partial\mathbf{k}\_{T}}\right)^{2} \times \left(\sigma\_{\mathbf{k}\_{T}}\right)^{2} \right] + \left[ \left(\frac{\partial\mathfrak{y}}{\partial\mathbf{n}\_{G}}\right)^{2} \times \left(\sigma\_{\mathbf{n}\_{G}}\right)^{2} \right] + \left[ \left(\frac{\partial\mathfrak{y}}{\partial\mathbf{n}\_{T}}\right)^{2} \times \left(\sigma\_{\mathbf{n}\_{T}}\right)^{2} \right] \right\} \tag{10}$$

where y represents RBE value

$$\mathcal{E}\left(\frac{\partial \mathbf{y}}{\partial k\_G}\right)^2 = \left\{ \left[ \frac{-\mathbf{1}}{\left(k\_G \mathbf{^2} \times D\_T\right)} \times \ln\left(\frac{n\_G}{n\_T}\right) \right] - \frac{k\_T}{k\_G} \right\}^2 \tag{11}$$

$$\left(\frac{\partial \mathbf{y}}{\partial k\_T}\right)^2 = \left(\frac{1}{k\_G}\right)^2\tag{12}$$

$$\left(\frac{\partial \mathbf{y}}{\partial n\_G}\right)^2 = \left(\frac{\mathbf{1}}{n\_G \times k\_G \times D\_T}\right)^2\tag{13}$$

convertant and data is presented in **Figure 3**. The doses 25 Gy, 75Gy and 100 Gy were selected and the results show a linear increase in gene conversion frequency with dose. In the case of proton radiation, at lower doses increase in gene conversion frequency was linear, whereas at higher doses it attains plateau. In the case of gamma radiation gene conversion frequency was linear throughout the selected dose region. The gene conversion frequency (G.C.F) for gamma and proton radiation were represented as G.C. F.gamma = (6.46 � 2.19) + (6.46 � 0.105) D (with R2 = 0.99) and G.C. F.Proton = (7.02 � 3.44) + (25.44 � 0.520) D (with R2 = 0.99). The RBE value of

*Gene conversion frequency after irradiating with proton (*●*) and gamma radiation (*■*).*

*Recent Techniques and Applications in Ionizing Radiation Research*

the proton radiation for gene conversion was calculated using slopes, is 3.93.

proton radiotherapy.

**8**

**Figure 3.**

**Relative biological effectiveness studies:** In the present study, along with cell inactivation and gene conversion studies, we conducted RBE studies for 3 MeV proton radiations. To estimate RBE value, the experiments were repeated using standard gamma radiation (**Figures 2** and **3**). Estimation of RBE value for proton beam is very important in medical treatment planning, where the RBE values should be known with at least 5–10% accuracy. Generally, a standard RBE value 1.1 is applied to the treatment plan. Recently many authors estimated RBE value for proton beam and they observed that there is a drastic change in RBE value near to Brag's-peak [16–30]. High energy protons have an RBE value of about 1.1, however, for low energy protons still sufficient data is not available to conclude the RBE value. In the present study, we used 3 MeV proton radiation, generally using such energy protons one can observe inside tumor during radiotherapy, so present contributions can be used to strengthen the literature data and can be used to improve

Presently RBE values are calculated on the basis of D0 doses, which give RBE value in the exponential region. In the present study, we formulated an equation, which can be used to calculate RBE value throughout the selected dose-region. Generally RBE is represented by taking the ratio between gamma radiation and test

At same biological effectiveness (6)

radiation doses, required to produce the same biological effectiveness.

RBE <sup>¼</sup> *DG DT*

*Recent Techniques and Applications in Ionizing Radiation Research*

$$\left(\frac{\partial \mathbf{y}}{\partial n\_T}\right)^2 = \left(\frac{1}{n\_T \times D\_T \times k\_G}\right)^2\tag{14}$$

derived from human epithelium tumors of the tongue and larynx, respectively, the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The RBE of the proton beams with LET 30 keV μm<sup>1</sup> was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively [18]. Similarly, Ristić-Fira et al. [29] reported RBE value for mid SOBP region proton particles using radio-

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem…*

*DOI: http://dx.doi.org/10.5772/intechopen.94243*

Recently, Wéra et al. [30] irradiated Human A549 alveolar adenocarcinoma cells with 4 MeV broad proton beam and calculated RBE value at 10% survival. They reported RBE value of the low energy proton radiation is independent of the dose rate and is equal to 1.9 0.4 for 10 keV <sup>μ</sup><sup>m</sup><sup>1</sup> and 2.9 0.5 for 25 keV <sup>μ</sup><sup>m</sup><sup>1</sup> [30]. In the same study they calculated RBE values at 77% survival level and were equal to 10.7 3.3 and 3.6 0.6 for 10 keV <sup>μ</sup><sup>m</sup><sup>1</sup> and 25 keV <sup>μ</sup><sup>m</sup><sup>1</sup> respectively [30]. These values suggest that RBE value depends on survival, which again depends on radiation dose. Britten et al. [22] studied human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and

200 MeV. Using Hep2 cells, the RBE values were 1.46 at the middle of SOBP, 2.3 at the distal end of the SOBP [22]. For V79 cells, the RBE for the 87 MeV beams was 1.23 for the proximal end of the SOBP, 1.46 for the distal SOBP and 1.78 for the distal end of the SOBP [22]. Similar studies were conducted by Paganetti [23], Słonina et al. [24] and Aoki-Nakano et al. [26] to calculate SOBP region RBE value. They concluded that, the proton RBE value increases with increasing LET which ranges from 1.1 to 4.98. The RBE values for continuous and pulsed proton radiation also studied using human tumor cells [27]. No significant difference was observed between pulsed proton (RBE = 1.22 0.19) and continuous proton (RBE = 1.10 0.1) beam [27].

Previous studies reveal that there is a large variation in reported RBE values among laboratories with the same cell line and a similar LET. For example, Belli et al. [16] and Folkard et al. [17] measured an RBE value of 24 keV μm<sup>1</sup> protons as 1.9 and 2.4, respectively. On average, literature reported data concludes RBE value for low energy proton radiation varies from 0.9 to 6, which is comparable with the

The study confirms that, the 3 MeV proton beam is more lethal to biological system compare to gamma radiation and the dose response was found to be linear. Nearly 4 times higher gene conversion frequency was observed in proton radiation as compared to gamma radiation. The estimated RBE value estimated from the mathematical equation developed in the present study is comparable with the experimental values. The RBE value of the 3 MeV protons was found to decreases with the dose and varied from 3.61 to 1.80. With the help of the present mathematical formulation, RBE value at any dose can be calculated in the exponential region of the survival curve without actually extending the experiment in that dose region,

The authors from Mangalore University are thankful to Board of Research in Nuclear Sciences, Department of Atomic Energy, Government of India, for the

which is not possible using conventional methods.

present findings.

**4. Conclusion**

**Acknowledgements**

financial support.

**11**

resistant human HTB140 melanoma cells and is found to be 2.09 0.36.

Accordingly standard deviation was calculated. **Figure 4** represents RBE value of 3 MeV proton beam at different doses, calculated using Eq. (9). The experimentally calculated RBE value and theoretically calculated RBE values were compared and presented in **Figure 4**. Very good correlation between experimental and theoretical data was observed.

Higher RBE values were observed at lower doses whereas remain constant at higher doses. RBE values varied in a range from 3.61 to 1.80; the maximum value at lower doses is mainly due to the absence of sub-lethal repair processes. In the case of gamma radiation, at lower doses induced damages are repaired but in the case of proton radiation a small dose also creates lethal damages, hence maximum RBE value was observed. At higher doses the damage due to peroxyl radicals and multi-ionizing events lead to lethal damage in gamma radiation, hence RBE value remains constant. Another reason for higher RBE value is energy deposition pattern of the 3 MeV proton radiation. The LET of the gamma radiation is 0.2–0.3 keV μm�<sup>1</sup> , whereas 3 MeV proton radiation is 13 keV μm�<sup>1</sup> . The higher RBE values for low energy protons were reported previously [16–30]. Belli et al. [16] has reported that the RBE depends on LET of the proton radiation. They studied SOBP region proton radiation using V79– 753B cells. The RBE value for protons with LET 7.7 keV μm�<sup>1</sup> , 11 keV μm�<sup>1</sup> , 20 keV μm�<sup>1</sup> , 30.5 keV μm�<sup>1</sup> , 34.6 keV <sup>μ</sup>m�<sup>1</sup> and 37.8 keV <sup>μ</sup>m�<sup>1</sup> is 2.22 � 0.27, 2.88 � 0.37, 3.64 � 0.41, 5.59 � 0.54, 5.06 � 0.51 and 4.50 � 0.44, respectively [16]. Similar type observation was made by Folkard et al. [17] and reported an RBE value for protons with mean energies of 1.9, 1.15 and 0.76 MeV, using V79 chinese hamster cells. The RBE values for cell survival at 10% survival level are 1.6, 1.9 and 3.36 for protons with track-average LETs of 17, 24 and 32 keV μm�<sup>1</sup> , respectively.

In another report Mark Andrew [28] observed an RBE value of 2.6 � 0.6 for 94 keV, 3.1 � 0.4 for 250 keV, 3.9 � 0.8 for 390 keV and 2.4 � 0.5 for 1.2 MeV protons using V79 cell line. Belli et al. [18] studied four human cell lines, SCC25, SQ20B

**Figure 4.** *Variation of RBE with dose; experimental (*●*) and theoretical (*■*).*

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem… DOI: http://dx.doi.org/10.5772/intechopen.94243*

derived from human epithelium tumors of the tongue and larynx, respectively, the normal lines M/10, derived from human mammary epithelium, and HF19 derived from a lung fibroblast. The RBE of the proton beams with LET 30 keV μm<sup>1</sup> was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19, respectively [18]. Similarly, Ristić-Fira et al. [29] reported RBE value for mid SOBP region proton particles using radioresistant human HTB140 melanoma cells and is found to be 2.09 0.36.

Recently, Wéra et al. [30] irradiated Human A549 alveolar adenocarcinoma cells with 4 MeV broad proton beam and calculated RBE value at 10% survival. They reported RBE value of the low energy proton radiation is independent of the dose rate and is equal to 1.9 0.4 for 10 keV <sup>μ</sup><sup>m</sup><sup>1</sup> and 2.9 0.5 for 25 keV <sup>μ</sup><sup>m</sup><sup>1</sup> [30]. In the same study they calculated RBE values at 77% survival level and were equal to 10.7 3.3 and 3.6 0.6 for 10 keV <sup>μ</sup><sup>m</sup><sup>1</sup> and 25 keV <sup>μ</sup><sup>m</sup><sup>1</sup> respectively [30]. These values suggest that RBE value depends on survival, which again depends on radiation dose. Britten et al. [22] studied human Hep2 laryngeal cancer cells and V79 cells at various positions along the SOBPs of beams with incident energies of 87 and 200 MeV. Using Hep2 cells, the RBE values were 1.46 at the middle of SOBP, 2.3 at the distal end of the SOBP [22]. For V79 cells, the RBE for the 87 MeV beams was 1.23 for the proximal end of the SOBP, 1.46 for the distal SOBP and 1.78 for the distal end of the SOBP [22]. Similar studies were conducted by Paganetti [23], Słonina et al. [24] and Aoki-Nakano et al. [26] to calculate SOBP region RBE value. They concluded that, the proton RBE value increases with increasing LET which ranges from 1.1 to 4.98. The RBE values for continuous and pulsed proton radiation also studied using human tumor cells [27]. No significant difference was observed between pulsed proton (RBE = 1.22 0.19) and continuous proton (RBE = 1.10 0.1) beam [27].

Previous studies reveal that there is a large variation in reported RBE values among laboratories with the same cell line and a similar LET. For example, Belli et al. [16] and Folkard et al. [17] measured an RBE value of 24 keV μm<sup>1</sup> protons as 1.9 and 2.4, respectively. On average, literature reported data concludes RBE value for low energy proton radiation varies from 0.9 to 6, which is comparable with the present findings.

#### **4. Conclusion**

*∂y ∂nT* <sup>2</sup>

*Recent Techniques and Applications in Ionizing Radiation Research*

radiation. The LET of the gamma radiation is 0.2–0.3 keV μm�<sup>1</sup>

753B cells. The RBE value for protons with LET 7.7 keV μm�<sup>1</sup>

protons with track-average LETs of 17, 24 and 32 keV μm�<sup>1</sup>

*Variation of RBE with dose; experimental (*●*) and theoretical (*■*).*

retical data was observed.

proton radiation is 13 keV μm�<sup>1</sup>

, 30.5 keV μm�<sup>1</sup>

20 keV μm�<sup>1</sup>

**Figure 4.**

**10**

<sup>¼</sup> <sup>1</sup>

Accordingly standard deviation was calculated. **Figure 4** represents RBE value of 3 MeV proton beam at different doses, calculated using Eq. (9). The experimentally calculated RBE value and theoretically calculated RBE values were compared and presented in **Figure 4**. Very good correlation between experimental and theo-

Higher RBE values were observed at lower doses whereas remain constant at higher doses. RBE values varied in a range from 3.61 to 1.80; the maximum value at lower doses is mainly due to the absence of sub-lethal repair processes. In the case of gamma radiation, at lower doses induced damages are repaired but in the case of proton radiation a small dose also creates lethal damages, hence maximum RBE value was observed. At higher doses the damage due to peroxyl radicals and multi-ionizing events lead to lethal damage in gamma radiation, hence RBE value remains constant. Another reason for higher RBE value is energy deposition pattern of the 3 MeV proton

reported previously [16–30]. Belli et al. [16] has reported that the RBE depends on LET of the proton radiation. They studied SOBP region proton radiation using V79–

2.88 � 0.37, 3.64 � 0.41, 5.59 � 0.54, 5.06 � 0.51 and 4.50 � 0.44, respectively [16]. Similar type observation was made by Folkard et al. [17] and reported an RBE value for protons with mean energies of 1.9, 1.15 and 0.76 MeV, using V79 chinese hamster cells. The RBE values for cell survival at 10% survival level are 1.6, 1.9 and 3.36 for

In another report Mark Andrew [28] observed an RBE value of 2.6 � 0.6 for 94 keV, 3.1 � 0.4 for 250 keV, 3.9 � 0.8 for 390 keV and 2.4 � 0.5 for 1.2 MeV protons using V79 cell line. Belli et al. [18] studied four human cell lines, SCC25, SQ20B

*nT* � *DT* � *kG* <sup>2</sup>

(14)

, whereas 3 MeV

,

, 11 keV μm�<sup>1</sup>

, respectively.

. The higher RBE values for low energy protons were

, 34.6 keV <sup>μ</sup>m�<sup>1</sup> and 37.8 keV <sup>μ</sup>m�<sup>1</sup> is 2.22 � 0.27,

The study confirms that, the 3 MeV proton beam is more lethal to biological system compare to gamma radiation and the dose response was found to be linear. Nearly 4 times higher gene conversion frequency was observed in proton radiation as compared to gamma radiation. The estimated RBE value estimated from the mathematical equation developed in the present study is comparable with the experimental values. The RBE value of the 3 MeV protons was found to decreases with the dose and varied from 3.61 to 1.80. With the help of the present mathematical formulation, RBE value at any dose can be calculated in the exponential region of the survival curve without actually extending the experiment in that dose region, which is not possible using conventional methods.

#### **Acknowledgements**

The authors from Mangalore University are thankful to Board of Research in Nuclear Sciences, Department of Atomic Energy, Government of India, for the financial support.

**References**

[1] Oliver J. The relative biological effectiveness of proton and ion beams. Z. Med.Phys. 2008;**18**(4):276-285

*DOI: http://dx.doi.org/10.5772/intechopen.94243*

enhancement ratio with radiation dose using Saccharomyces cerevisiae. Journal

[10] Joseph P, Acharya S, Sanjeev G, Bhat NN, Narayana Y. Cell inactivation studies on yeast cells under euoxic and hypoxic condition using electron beam from microtron accelerator. Journal of Radioanalytical and Nuclear Chemistry.

[11] Joseph P, Nairy R, Acharya S, Ganesh S, Narayana Y. Chemical dosimeters for electron beam dosimetry of microtron accelerator. Journal of Radioanalytical and Nuclear Chemistry.

[12] Chaurasiaa KR, Balakrishnana S, Kunwarb A, Yadav U, Bhat N, Anjariaa K, et al. Cyto-genotoxicity

radioprotector,3,3-diselenodipropionic acid (DSePA) in Chinese hamster ovary (CHO) cells and human peripheral blood lymphocytes. Mutation Research/ Genetic Toxicology and Environmental

of Radioanalytical and Nuclear Chemistry. 2014;**302**:1027-1033

2011;**290**(1):209-214

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem…*

2014;**302**:1013-1019

assessment of potential

Mutagenesis. 2014;**774**:8-16

**34**(4):221-224

[13] Joseph P, Narayana Y, Nairy R, Ganesh S, Bhat NN. Assessment of electron and gamma induced DNA damage in human peripheral blood by alkaline comet assay. Radiation Protection and Environment. 2011;

[14] Nairy RK, Bhat NN, Joseph P, Sanjeev G, Yerol N. Studies on electron beam induced DNA damage and repair kinetics in lymphocytes by alkaline comet assay. Int. Journal of Radiation

Research. 2015;**13**(3):213-220

[15] Nairy RK, Bhat NN, Joseph P, Sanjeev G, Yerol N. Dose response study using Micronuclueus cytome assay-a tool for biodosimtry application. Radiation Protection Dosimetry. 2016

[2] Singh P. Folded tandem ion

2011;**79**(2):559-562

R109

283-315

3925-3930

1439-1443

1968.

**13**

accelerator facility at BARC. Pramana-Journal de Physique. 2001;**57**:639

[3] Kim SS, Choo DW, Shin D, Baek HJ, Kim TH, Motoyama N, et al. In vivo radiobiological characterization of proton beam at the National Cancer Center in Korea: Effect of the Chk2 mutation. International Journal of Radiation Oncology, Biology, Physics.

[4] Nikjoo H, Lindborg L. RBE of low energy electrons and photons. Physics in Medicine and Biology. 2010;**55**(10):R65-

[5] Johnson A, O'Donnell M. Cellular DNA replicases: Components and dynamics at the replication fork. Annual Review of Biochemistry. 2005;**74**:

[6] Yuen KW, Warren CD, Chen O, Kwok T, Hieter P, Spencer FA.

[7] Botstein D, Fink GR. Yeast: An experimental organism for modern biology. Science. 1988;**240**(4858):

[8] Fricke H, Hart E J, In; Radiation Dosimetry, Vol II, Eds. Allix F. H. and S. C. Academy Press, W. C. New York,

[9] Nairy R, Bhat NN, Anjaria KB, Sreedevi B, Sapra BK, Narayana Y. Study of gamma radiation induced damages and variation of oxygen

Systematic genome instability screens in yeast and their potential relevance to cancer. Proceedings of the National Academy of Sciences of the United States of America. 2007;**104**(10):

#### **Author details**

Rajesha K. Nairy<sup>1</sup> \*, Nagesh N. Bhat2 , K.B. Anjaria<sup>2</sup> , Usha Yadav<sup>2</sup> , Rajesh Chaurasia<sup>2</sup> , Kapil Shirsath<sup>2</sup> , Utkarsha Desai<sup>2</sup> , S.K. Gupta<sup>3</sup> , B.K. Sapra<sup>2</sup> and Narayana Yerol<sup>4</sup>

1 Department of Physics, P.C. Jabin Science College, 580031, Hubballi, Karnataka, India

2 RP and AD, Bhabha Atomic Research Center, 400085, Mumbai, India

3 IADD, Bhabha Atomic Research Centre, 400085, Mumbai, India

4 Department of studies in Physics, Mangalore University, 574 199, Mangalagangotri, India

\*Address all correspondence to: rajesh.nairy@gmail.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem… DOI: http://dx.doi.org/10.5772/intechopen.94243*

#### **References**

[1] Oliver J. The relative biological effectiveness of proton and ion beams. Z. Med.Phys. 2008;**18**(4):276-285

[2] Singh P. Folded tandem ion accelerator facility at BARC. Pramana-Journal de Physique. 2001;**57**:639

[3] Kim SS, Choo DW, Shin D, Baek HJ, Kim TH, Motoyama N, et al. In vivo radiobiological characterization of proton beam at the National Cancer Center in Korea: Effect of the Chk2 mutation. International Journal of Radiation Oncology, Biology, Physics. 2011;**79**(2):559-562

[4] Nikjoo H, Lindborg L. RBE of low energy electrons and photons. Physics in Medicine and Biology. 2010;**55**(10):R65- R109

[5] Johnson A, O'Donnell M. Cellular DNA replicases: Components and dynamics at the replication fork. Annual Review of Biochemistry. 2005;**74**: 283-315

[6] Yuen KW, Warren CD, Chen O, Kwok T, Hieter P, Spencer FA. Systematic genome instability screens in yeast and their potential relevance to cancer. Proceedings of the National Academy of Sciences of the United States of America. 2007;**104**(10): 3925-3930

[7] Botstein D, Fink GR. Yeast: An experimental organism for modern biology. Science. 1988;**240**(4858): 1439-1443

[8] Fricke H, Hart E J, In; Radiation Dosimetry, Vol II, Eds. Allix F. H. and S. C. Academy Press, W. C. New York, 1968.

[9] Nairy R, Bhat NN, Anjaria KB, Sreedevi B, Sapra BK, Narayana Y. Study of gamma radiation induced damages and variation of oxygen

enhancement ratio with radiation dose using Saccharomyces cerevisiae. Journal of Radioanalytical and Nuclear Chemistry. 2014;**302**:1027-1033

[10] Joseph P, Acharya S, Sanjeev G, Bhat NN, Narayana Y. Cell inactivation studies on yeast cells under euoxic and hypoxic condition using electron beam from microtron accelerator. Journal of Radioanalytical and Nuclear Chemistry. 2011;**290**(1):209-214

[11] Joseph P, Nairy R, Acharya S, Ganesh S, Narayana Y. Chemical dosimeters for electron beam dosimetry of microtron accelerator. Journal of Radioanalytical and Nuclear Chemistry. 2014;**302**:1013-1019

[12] Chaurasiaa KR, Balakrishnana S, Kunwarb A, Yadav U, Bhat N, Anjariaa K, et al. Cyto-genotoxicity assessment of potential radioprotector,3,3-diselenodipropionic acid (DSePA) in Chinese hamster ovary (CHO) cells and human peripheral blood lymphocytes. Mutation Research/ Genetic Toxicology and Environmental Mutagenesis. 2014;**774**:8-16

[13] Joseph P, Narayana Y, Nairy R, Ganesh S, Bhat NN. Assessment of electron and gamma induced DNA damage in human peripheral blood by alkaline comet assay. Radiation Protection and Environment. 2011; **34**(4):221-224

[14] Nairy RK, Bhat NN, Joseph P, Sanjeev G, Yerol N. Studies on electron beam induced DNA damage and repair kinetics in lymphocytes by alkaline comet assay. Int. Journal of Radiation Research. 2015;**13**(3):213-220

[15] Nairy RK, Bhat NN, Joseph P, Sanjeev G, Yerol N. Dose response study using Micronuclueus cytome assay-a tool for biodosimtry application. Radiation Protection Dosimetry. 2016

**Author details**

Rajesha K. Nairy<sup>1</sup>

Mangalagangotri, India

Kapil Shirsath<sup>2</sup>

India

**12**

\*, Nagesh N. Bhat2

*Recent Techniques and Applications in Ionizing Radiation Research*

, Utkarsha Desai<sup>2</sup>

, K.B. Anjaria<sup>2</sup>

1 Department of Physics, P.C. Jabin Science College, 580031, Hubballi, Karnataka,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, S.K. Gupta<sup>3</sup>

2 RP and AD, Bhabha Atomic Research Center, 400085, Mumbai, India

3 IADD, Bhabha Atomic Research Centre, 400085, Mumbai, India

4 Department of studies in Physics, Mangalore University, 574 199,

\*Address all correspondence to: rajesh.nairy@gmail.com

provided the original work is properly cited.

, Usha Yadav<sup>2</sup>

, B.K. Sapra<sup>2</sup> and Narayana Yerol<sup>4</sup>

, Rajesh Chaurasia<sup>2</sup>

,

[16] Belli M, Cera F, Cherubini R, Dalla Vecchia M, Haque AMI, Ianzini F, et al. RBE–LET relationships for cell inactivation and mutation induced by low energy protons in V79 cells: Further results at the LNL facility. International Journal of Radiation Biology. 1998;**74**: 501-509

[17] Folkard M, Prise KM, Vojnovic B, Davies S, Roper MJ, Michael BD. The irradiation of V79 mammalian cells by protons with energies below 2 MeV. Part I: Experimental arrangement and measurements of cell survival. International Journal of Radiation Biology. 1989;**56**(3):221-237

[18] Belli M, Bettega D, Calzolari P, Cera F, Cherubini R, Dalla Vecchia M, et al. Inactivation of human normal and tumour cells irradiated with low energy protons. International Journal of Radiation Biology. 2000;**76**(6):831-839

[19] Bettega D, Calzolari P, Chauvel P, Courdi A, Herault J, Iborra N, et al. Radiobiological studies on the 65 MeV therapeutic proton beam at Nice using human tumour cells. International Journal of Radiation Biology. 2000; **76**(10):1297-1303

[20] Paganetti H, Niemierko A, Ancukiewicz M, Gerweck LE, Goitein M, Loeffler JS, et al. Relative biological effectiveness (RBE) values for proton beam therapy. International Journal of Radiation Oncology, Biology, Physics. 2002;**53**(2):407-421

[21] Butterworth KT, McGarry CK, Clasie B, Carabe-Fernandez A, Schuemann J, Depauw N, et al. Relative biological effectiveness (RBE) and outof-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries. Physics in Medicine and Biology. 2012;**57**(20): 6671-6680

[22] Britten RA, Nazaryan V, Davis LK, Klein SB, Nichiporov D, Mendonca MS, et al. Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam. Radiation Research. 2013;**179**(1):21-28

Response of human HTB140 melanoma cells to conventional radiation and hadrons. Physiological Research. 2011;

*DOI: http://dx.doi.org/10.5772/intechopen.94243*

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem…*

[30] Wéra AC, Heuskin AC, Riquier H, Michiels C, Lucas S. Low-LET proton irradiation of A549 non-small cell lung adenocarcinoma cells:Dose response and RBE determination. Radiation Research.

**60**(1):S129-S135

2013;**179**(3):273-281

**15**

[23] Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Physics in Medicine and Biology. 2014;**59**(22):R419-R472

[24] Słonina D, Biesaga B, Swakoń J, Kabat D, Grzanka L, Ptaszkiewicz M, et al. Relative biological effectiveness of the 60-MeV therapeutic proton beam at the Institute of Nuclear Physics. (IFJ PAN) in Kraków, Poland. Radiation and Environmental Biophysics. 2014;**53**(4): 745-754

[25] Matsumoto Y, Matsuura T, Wada M, Egashira Y, Nishio T, Furusawa Y. Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study. Journal of Radiation Research. 2014;**55**(4):816-822

[26] Aoki-Nakano M, Furusawa Y, Uzawa A, Matsumoto Y, Hirayama RT, suruoka C, et al. Relative biological effectiveness of therapeutic proton beams for HSG cells at Japanese proton therapy facilities. Journal of Radiation Research. 2014;**55**(4):812-815

[27] Zlobinskaya O, Siebenwirth C, Greubel C, Hable V, Hertenberger R, Humble N, et al. The effects of ultrahigh dose rate proton irradiation on growth delay in the treatment of human tumor xenografts in nude mice. Radiation Research. 2014;**181**(2):177-183

[28] Mark Andrew S. Fast neutron relative biological effectiveness determination via proton bombardment of V79 cells master of science thesis submitted to Massachusetts institute of. Technology. 1996

[29] Ristić-Fira A, Todorović D, Zakula J, Keta O, Cirrone P, Cuttone G, et al.

*Relative Biological Effectiveness Studies Using 3 MeV Proton Beam from Folded Tandem… DOI: http://dx.doi.org/10.5772/intechopen.94243*

Response of human HTB140 melanoma cells to conventional radiation and hadrons. Physiological Research. 2011; **60**(1):S129-S135

[16] Belli M, Cera F, Cherubini R, Dalla Vecchia M, Haque AMI, Ianzini F, et al.

*Recent Techniques and Applications in Ionizing Radiation Research*

et al. Variations in the RBE for cell killing along the depth-dose profile of a modulated proton therapy beam. Radiation Research. 2013;**179**(1):21-28

[23] Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Physics in Medicine and

Biology. 2014;**59**(22):R419-R472

[25] Matsumoto Y, Matsuura T, Wada M, Egashira Y, Nishio T, Furusawa Y. Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study. Journal of Radiation Research. 2014;**55**(4):816-822

[26] Aoki-Nakano M, Furusawa Y, Uzawa A, Matsumoto Y, Hirayama RT, suruoka C, et al. Relative biological effectiveness of therapeutic proton beams for HSG cells at Japanese proton therapy facilities. Journal of Radiation

Research. 2014;**55**(4):812-815

[27] Zlobinskaya O, Siebenwirth C, Greubel C, Hable V, Hertenberger R, Humble N, et al. The effects of ultrahigh dose rate proton irradiation on growth delay in the treatment of human

tumor xenografts in nude mice.

[28] Mark Andrew S. Fast neutron relative biological effectiveness

Technology. 1996

Radiation Research. 2014;**181**(2):177-183

determination via proton bombardment of V79 cells master of science thesis submitted to Massachusetts institute of.

[29] Ristić-Fira A, Todorović D, Zakula J, Keta O, Cirrone P, Cuttone G, et al.

745-754

[24] Słonina D, Biesaga B, Swakoń J, Kabat D, Grzanka L, Ptaszkiewicz M, et al. Relative biological effectiveness of the 60-MeV therapeutic proton beam at the Institute of Nuclear Physics. (IFJ PAN) in Kraków, Poland. Radiation and Environmental Biophysics. 2014;**53**(4):

[17] Folkard M, Prise KM, Vojnovic B, Davies S, Roper MJ, Michael BD. The irradiation of V79 mammalian cells by protons with energies below 2 MeV. Part I: Experimental arrangement and measurements of cell survival. International Journal of Radiation Biology. 1989;**56**(3):221-237

[18] Belli M, Bettega D, Calzolari P, Cera F, Cherubini R, Dalla Vecchia M, et al. Inactivation of human normal and tumour cells irradiated with low energy protons. International Journal of Radiation Biology. 2000;**76**(6):831-839

[19] Bettega D, Calzolari P, Chauvel P, Courdi A, Herault J, Iborra N, et al. Radiobiological studies on the 65 MeV therapeutic proton beam at Nice using human tumour cells. International Journal of Radiation Biology. 2000;

**76**(10):1297-1303

6671-6680

**14**

[20] Paganetti H, Niemierko A, Ancukiewicz M, Gerweck LE, Goitein M, Loeffler JS, et al. Relative biological effectiveness (RBE) values for proton beam therapy. International Journal of Radiation Oncology, Biology,

Physics. 2002;**53**(2):407-421

[21] Butterworth KT, McGarry CK, Clasie B, Carabe-Fernandez A,

Schuemann J, Depauw N, et al. Relative biological effectiveness (RBE) and outof-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries. Physics in Medicine and Biology. 2012;**57**(20):

[22] Britten RA, Nazaryan V, Davis LK, Klein SB, Nichiporov D, Mendonca MS,

RBE–LET relationships for cell inactivation and mutation induced by low energy protons in V79 cells: Further results at the LNL facility. International Journal of Radiation Biology. 1998;**74**:

501-509

[30] Wéra AC, Heuskin AC, Riquier H, Michiels C, Lucas S. Low-LET proton irradiation of A549 non-small cell lung adenocarcinoma cells:Dose response and RBE determination. Radiation Research. 2013;**179**(3):273-281

**Chapter 2**

**Abstract**

directly with the LQ S(n,D).

**1. Introduction**

**17**

(RBEf)?

Biologically Effective Dose (BED)

The current radiosensitive studies are described with linear-quadratic (LQ) cell survival (S) model for one fraction with a dose d. As result of assuming all sublethally damaged cells (SLDCs) are completely repaired during the interfractions, that is, no presence of SLDCs, the survived cells are calculated for a n-fractionated regimen with the LQ S(n,D) model. A mathematically processed subpart of LQS(n,D) is the biologically effective dose (BED) that is used for evaluating a so-called "biological dose." The interactions of ionizing radiation with a living tissue can produce partial death or sublethal damage from healthy or sublethally damaged cells. The proportions of the killed and sub-lethally damaged cells define the radiation biological effects (RBEfs). Computational simulations using RBEFs for fractionated regimens let calculating tumor control probability. While the derivation of the LQ S(n,D) considers a 100% cell repair, that is, 0% of sublethally damaged cells (SLDCs), the radiobiological simulators take into account the presence of SLDCs, as well as a cell repair <100% during the interfractions and interruption. Given "biological dose" does not exist, but RBEf, there was need for creating the BED. It is shown how some uses of BED, like the derivation of EQ2D expression, can be done

**Keywords:** BED, simulation, radiotherapy, brachytherapy, fractionation,

In 1989, an article published in [1] introduced the term BED, biologically effective dose, as a linear-quadratic (LQ)-based formula. After 21 years, a new article was published in [2] for showing the wide use of BED in the radiation therapies. In this work, the BED was defined (of a given schedule) as: "the total dose required to give the same log cell kill as the schedule being studied, at an infinitely low doserate or with infinitely small fractions well-spaced out; now with an overall time

When ionizing radiation interacts with a determined volume of living tissue, this can or cannot interact with all cells, can or cannot produce effects as result of their interactions; and the first fraction of a fractionated treatment produces a partial number of killed and sublethally damaged cells (SLDCs) from the total initially

linear-quadratic model, mathematical models, radiobiology

factor for repopulation during continued irradiation."

or Radiation Biological Effect

*Terman Frometa-Castillo, Anil Pyakuryal, Amadeo Wals-Zurita and Asghar Mesbahi*

#### **Chapter 2**

## Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)?

*Terman Frometa-Castillo, Anil Pyakuryal, Amadeo Wals-Zurita and Asghar Mesbahi*

#### **Abstract**

The current radiosensitive studies are described with linear-quadratic (LQ) cell survival (S) model for one fraction with a dose d. As result of assuming all sublethally damaged cells (SLDCs) are completely repaired during the interfractions, that is, no presence of SLDCs, the survived cells are calculated for a n-fractionated regimen with the LQ S(n,D) model. A mathematically processed subpart of LQS(n,D) is the biologically effective dose (BED) that is used for evaluating a so-called "biological dose." The interactions of ionizing radiation with a living tissue can produce partial death or sublethal damage from healthy or sublethally damaged cells. The proportions of the killed and sub-lethally damaged cells define the radiation biological effects (RBEfs). Computational simulations using RBEFs for fractionated regimens let calculating tumor control probability. While the derivation of the LQ S(n,D) considers a 100% cell repair, that is, 0% of sublethally damaged cells (SLDCs), the radiobiological simulators take into account the presence of SLDCs, as well as a cell repair <100% during the interfractions and interruption. Given "biological dose" does not exist, but RBEf, there was need for creating the BED. It is shown how some uses of BED, like the derivation of EQ2D expression, can be done directly with the LQ S(n,D).

**Keywords:** BED, simulation, radiotherapy, brachytherapy, fractionation, linear-quadratic model, mathematical models, radiobiology

#### **1. Introduction**

In 1989, an article published in [1] introduced the term BED, biologically effective dose, as a linear-quadratic (LQ)-based formula. After 21 years, a new article was published in [2] for showing the wide use of BED in the radiation therapies. In this work, the BED was defined (of a given schedule) as: "the total dose required to give the same log cell kill as the schedule being studied, at an infinitely low doserate or with infinitely small fractions well-spaced out; now with an overall time factor for repopulation during continued irradiation."

When ionizing radiation interacts with a determined volume of living tissue, this can or cannot interact with all cells, can or cannot produce effects as result of their interactions; and the first fraction of a fractionated treatment produces a partial number of killed and sublethally damaged cells (SLDCs) from the total initially

undamaged ones. During the second and successive fractions, the radiation can interact with these three kinds of cells, where the interactions can produce the same effects of the first fraction from the undamaged cells and SLDCs.

*Cell kill* <sup>¼</sup> *<sup>E</sup>* <sup>¼</sup> *<sup>n</sup> <sup>α</sup><sup>d</sup>* <sup>þ</sup> *<sup>β</sup>d*<sup>2</sup> (4)

*E* ¼ *nαd* ¼ *αD* (5)

*BED* ¼ *D* ¼ *E=α* (6)

¼ 140*Gy*1*:*<sup>5</sup> (7)

*LQS n*ð Þ¼ 1, *D*<sup>1</sup> *LQS n*ð Þ 2, *D*<sup>2</sup> (8)

2.Consider a progressive reduction in d such that it approaches a value of zero. Although the number of fractions n will then need to be increased to maintain the same effect, βd2 will be very small in comparison with ad (since d will greatly exceed d2 for very small values and α always exceeds β). Therefore,

3.This demonstrates that the total dose (D) of radiotherapy given at a very low dose per fraction represents the highest total dose required to obtain a specific effect. The total dose required in these conditions constitutes the definition of BED in situations where cellular repopulation can be ignored, that is, in this

The authors of [4] considered that: "BED represents the physical dose required

The procedure used in [4] is purely mathematical, since the cell kill (K) and its complement, the cell survival (S), are stochastic effects with a deterministic region for low values of d, where D does not produce any effect, that is, there will be 100%

To date, except the probabilistic treatments of the tumor control/normal tissue complication probability (TCP/NTCP), many stochastic processes/effects in areas of the ionizing radiations interacting with living tissues have not been probabilistically treated nor modeled, which has led deficiencies, like replacement in the evaluations of cell survival (S)—a probabilistic metric—by BED, a non-probabilistic,

In [4], the authors have shown the use of BED in practical situations for normal

tissues. For example, if a dose of 60 Gy in 30 fractions is received by a critical normal tissue, the associated BED may (for example) be expressed in terms of Gy1.5, Gy2, and Gy3 (for α/β ratios of 1.5, 2, and 3 Gy). The initial BED value for a fractionation schedule of 60 Gy in 30 fractions (BED = 140Gy1.5) is used to calculate the total dose and dose per fraction for the alternative schedule of 20 fractions. The result for alternative fractionation schedule is obtained from the solution of d in a

> *d* 1*:*5

Really, we can use the Eq. (2) for determining the previous alternative fractionation schedule (n2 fractions and d2 dose per fractions) without need of creating the

20*d* 1 þ

for a given effect if the dose were to be delivered by infinitely small doses per fraction or, in the case of continuous radiation rates, at a very low dose rate."

when d is very small, Eq. (4) is approximated as

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)?*

*DOI: http://dx.doi.org/10.5772/intechopen.92029*

a mathematical derivation from the LQ S(n,D) formalism.

limiting case:

of S; i.e. 0% of K.

**2.1 The BED in radiotherapy**

rearrangement of following equation

BED, based on the following procedure

**19**

BED has direct relationship with the radiation biological effects (RBEfs), in particular the cell survival (S) in radiation treatments with n fractions, d dose per fractions delivered in tissues characterized with LQ parameters α and α/β. The BED expression was a result of a mathematical derivation of the exponential part of the LQ S model for treatments with n fractions and dose per fraction d, the LQ S(n,D) where D = nd; and this model was obtained assuming that all sublethally damaged cells are wholly repaired during the interfraction period.

"BED is a measure of the true biological dose delivered by a particular combination of dose per fraction and total dose to a particular tissue characterized by a specific α/β ratio" [3]. This expression is incoherent because only the physical dose is delivered, and produces biological effects. There is no "biological dose."

The mathematical formulas have traditionally been used for calculating physical quantifications of deterministic and stochastic processes/effects (SP/Es). At this time there is high development in the computer science, where the computational simulators allow us determining probabilistic metrics some SP/Es, such as their means and probabilities, based on simulations of many possible cases.

The RBEfs should be estimated with computational radiobiological simulators or with the current LQ S(n,D) model.

#### **2. The biologically effective dose (BED)**

Nowadays, the radiosensitivity studies function of the absorbed dose (d) are described with the cell survival (S), which is complement of cell kill (K), and probabilistically S = 1-K. These studies are widely modeled with the LQ S(d) for one fraction as

$$LQS(d) = \exp\left(-ad - \beta d^2\right) \tag{1}$$

where α and β are the LQ parameters.

d: dose of one fraction.

As result of assuming all sublethally damaged cells (SLDCs) are completely repaired during the interfractions, that is, no presence of SLDCs, the survived cells are calculated for a n-fractionated regimen as

$$LQS(n, D) = [LQ \ S(d)]^n = \exp\left(-aD - \beta D^2/n\right) \tag{2}$$

where D = n\*d.

A mathematically processed subpart of LQ S(n,D) is the BED that is used for evaluating a called "biological dose," and is written as

$$BED = D\left[\mathbf{1} + \frac{d}{\ast \prime\_{\beta}}\right] \tag{3}$$

As an inherent part of the LQ S(n,D) model, the origin of BED is explained in [4] the following way.

1.The radiation cell kill (or effect, E) can be expressed as

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)? DOI: http://dx.doi.org/10.5772/intechopen.92029*

$$\text{Cell } kill = \text{E} = n \left( ad + \beta d^2 \right) \tag{4}$$

2.Consider a progressive reduction in d such that it approaches a value of zero. Although the number of fractions n will then need to be increased to maintain the same effect, βd2 will be very small in comparison with ad (since d will greatly exceed d2 for very small values and α always exceeds β). Therefore, when d is very small, Eq. (4) is approximated as

$$E = nad = aD\tag{5}$$

3.This demonstrates that the total dose (D) of radiotherapy given at a very low dose per fraction represents the highest total dose required to obtain a specific effect. The total dose required in these conditions constitutes the definition of BED in situations where cellular repopulation can be ignored, that is, in this limiting case:

$$BED = D = E/a \tag{6}$$

The authors of [4] considered that: "BED represents the physical dose required for a given effect if the dose were to be delivered by infinitely small doses per fraction or, in the case of continuous radiation rates, at a very low dose rate."

The procedure used in [4] is purely mathematical, since the cell kill (K) and its complement, the cell survival (S), are stochastic effects with a deterministic region for low values of d, where D does not produce any effect, that is, there will be 100% of S; i.e. 0% of K.

To date, except the probabilistic treatments of the tumor control/normal tissue complication probability (TCP/NTCP), many stochastic processes/effects in areas of the ionizing radiations interacting with living tissues have not been probabilistically treated nor modeled, which has led deficiencies, like replacement in the evaluations of cell survival (S)—a probabilistic metric—by BED, a non-probabilistic, a mathematical derivation from the LQ S(n,D) formalism.

#### **2.1 The BED in radiotherapy**

In [4], the authors have shown the use of BED in practical situations for normal tissues. For example, if a dose of 60 Gy in 30 fractions is received by a critical normal tissue, the associated BED may (for example) be expressed in terms of Gy1.5, Gy2, and Gy3 (for α/β ratios of 1.5, 2, and 3 Gy). The initial BED value for a fractionation schedule of 60 Gy in 30 fractions (BED = 140Gy1.5) is used to calculate the total dose and dose per fraction for the alternative schedule of 20 fractions. The result for alternative fractionation schedule is obtained from the solution of d in a rearrangement of following equation

$$120d\left(1+\frac{d}{1.5}\right) = 140Gy\_{1.5} \tag{7}$$

Really, we can use the Eq. (2) for determining the previous alternative fractionation schedule (n2 fractions and d2 dose per fractions) without need of creating the BED, based on the following procedure

$$L\mathbb{Q}\mathbb{S}(n\_1, D\_1) = L\mathbb{Q}\mathbb{S}(n\_2, D\_2) \tag{8}$$

undamaged ones. During the second and successive fractions, the radiation can interact with these three kinds of cells, where the interactions can produce the same

BED has direct relationship with the radiation biological effects (RBEfs), in particular the cell survival (S) in radiation treatments with n fractions, d dose per fractions delivered in tissues characterized with LQ parameters α and α/β. The BED expression was a result of a mathematical derivation of the exponential part of the LQ S model for treatments with n fractions and dose per fraction d, the LQ S(n,D) where D = nd; and this model was obtained assuming that all sublethally damaged

"BED is a measure of the true biological dose delivered by a particular combina-

The mathematical formulas have traditionally been used for calculating physical quantifications of deterministic and stochastic processes/effects (SP/Es). At this time there is high development in the computer science, where the computational simulators allow us determining probabilistic metrics some SP/Es, such as their

The RBEfs should be estimated with computational radiobiological simulators or

Nowadays, the radiosensitivity studies function of the absorbed dose (d) are described with the cell survival (S), which is complement of cell kill (K), and probabilistically S = 1-K. These studies are widely modeled with the LQ S(d) for one

As result of assuming all sublethally damaged cells (SLDCs) are completely repaired during the interfractions, that is, no presence of SLDCs, the survived cells

*LQS n*ð Þ¼ , *<sup>D</sup>* ½ � *LQ S d*ð Þ *<sup>n</sup>* <sup>¼</sup> *exp* �*α<sup>D</sup>* � *<sup>β</sup>D*<sup>2</sup>

*BED* ¼ *D* 1 þ

A mathematically processed subpart of LQ S(n,D) is the BED that is used for

*d* ∝*=β*

As an inherent part of the LQ S(n,D) model, the origin of BED is explained in [4]

*LQS d*ð Þ¼ *exp* �*α<sup>d</sup>* � *<sup>β</sup>d*<sup>2</sup> (1)

*=n* (2)

(3)

tion of dose per fraction and total dose to a particular tissue characterized by a specific α/β ratio" [3]. This expression is incoherent because only the physical dose

is delivered, and produces biological effects. There is no "biological dose."

means and probabilities, based on simulations of many possible cases.

effects of the first fraction from the undamaged cells and SLDCs.

*Recent Techniques and Applications in Ionizing Radiation Research*

cells are wholly repaired during the interfraction period.

with the current LQ S(n,D) model.

fraction as

**2. The biologically effective dose (BED)**

where α and β are the LQ parameters.

are calculated for a n-fractionated regimen as

evaluating a called "biological dose," and is written as

1.The radiation cell kill (or effect, E) can be expressed as

d: dose of one fraction.

where D = n\*d.

the following way.

**18**

where *D1 = n1d1* and *D2 = n2d2*

$$\exp\left(-aD\_1 - \beta D\_1^{\;\;2}/n\_1\right) = \exp\left(-aD\_2 - \beta D\_2^{\;\;2}/n\_1\right) \tag{9}$$

$$-aD\_1 - \beta D\_1^{\ 2}/n\_2 = -aD\_2 - \beta D\_2^{\ 2}/n\_1\tag{10}$$

*2.1.1 The BED in interrupted treatments*

*DOI: http://dx.doi.org/10.5772/intechopen.92029*

**2.2 The BED in brachytherapy (BT)**

compensating the interruption) are considered.

(Pt). These inclusions are notary in the BT as shown in [9].

The Pt effect is considered in the BED expression as:

**3. The radiation biological effect (RBEf)**

like the cell repopulation.

dimensionless factor RE as

MDR, or LDR.

this model.

**21**

Many of the current works, such as [5–8] related with the interrupted treatment use directly the BED expression or with some modifications that involve elements,

The BT may be delivered at high, medium, or low dose rates, respectively HDR,

Within of the BED expression, they have tried of including other factors affecting the RBEfs, such as cell sublethal damage (SL), cell repair (Rt), and repopulation

The works of [9–11] are strongly based on the BED. Here the factors affecting RBEf are added in the BED expression or included in its dimensionless subpart, the RE. More than 16 equations modifying Eq. (17) have been developed in this work.

where T is the overall time, Tdelay is the delay time after the beginning of treatment before the repopulation rate becomes significant, and K is a parameter of

radioactive sources is incorporated in the factor RE of Eq. (17) as

radiation interactions with the cells are probabilistically related as

*RE* ¼ 1 þ

where R0 is the initial dose rate, and λ is the radionuclide decay constant.

After the first fraction of irradiation to a living tissue region with a dose d, a number of killed and sublethally damaged cells appear. The mean outcomes of the

The Rt effect for a continuous low dose rate is considered into RE as a complex expression in [9]. In the same reference, for permanent implant, the decay of the

> *R*0 ð Þ *μ* þ *λ <sup>α</sup>*

*=β*

*K* þ *SL* þ *U* ¼ 1 100% ð Þ (21)

*S* ¼ *SL* þ *U* (22) *K* þ *S* ¼ 1 100% ð Þ (23)

*BED* ¼ *D* ∗ RE*:* (17)

*BED* ¼ *D* ∗ *RE* � *RCF* (18) *RCF* <sup>¼</sup> *<sup>K</sup>* <sup>∗</sup> *<sup>T</sup>* � *Tdelay* (19)

(20)

The BED is also expressed as the product of the total physical dose (D) and a

The BED is one of the most current important tools for compensating interrupted radiation treatments, where, as described in [5] three values of BED (original for the initial prescription, applied before the interruption and a new for

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)?*

On multiplication of Eq. (10) by �1/α, then

$$n\_1 d\_1 + n\_1 \frac{d\_1^{\;^2}}{\!\!\!a^{\prime}\_{\beta}} = n\_2 d\_2 + n\_2 \frac{d\_2^{\;^2}}{\!\!\!a^{\prime}\_{\beta}} \tag{11}$$

Substituting n1 = 30, d1 = 2 Gy (D1 = n1d1 = 60 Gy), and n2 = 20, we obtain the same Eq. (7) but without the dimension *Gy1.5*

$$20d\left(1+\frac{d}{1.5}\right) = 140\tag{12}$$

From the Eq. (11) one can derive the current equivalent dose in 2-Gy fractions (EQD2) in Gy, that is, the Eq. (14), if one substitutes n1 = n2 and d2 = 2Gy transform the Eq. (11) as

$$D\_1 + D\_1 \frac{2Gy}{a\_{\!/\partial}} = D\_2 + D\_2 \frac{d}{a\_{\!/\partial}} \tag{13}$$

where *D1 = EQD2* and *D2 = D = nd,* then

$$\text{EQD2} = \text{D}(d + a/\beta)/(\text{2Gy} + a/\beta) \tag{14}$$

This derivation does not need creation of the BED.

With the introduction of BED in radiotherapy, the radiation biological effects of radiation treatments have been characterized with BED with generic values α/β = 10 Gy for tumors and α/β = 3 Gy for normal tissues.

While the BED expression, the Eq. (3), has only one parameter, α/β, the LQS(n,D) has two: α and β. Therefore, a tissue with α = 1 Gy�<sup>1</sup> and α/β = 10 Gy that receives 60 Gy in 30 fractions, that is, d = 2 Gy, will have a biological radiation effect of 9.1% of cell survival.

The cell repopulation (CR) has been introduced in Eq. (3) as

$$BED = D\left[\mathbf{1} + \frac{d}{\mathbf{s}\prime\_{\beta}}\right] - \mathbf{K}(\mathbf{T} - T\_K) \tag{15}$$

where T is the overall treatment duration.

Tk is the time when the cell repopulation starts.

K is the factor in Gy/day. According to [4], it is the daily BED equivalent of repopulation.

The CR can be introduced in Eq. (2) as

$$LQS(n, D) = \exp\left(-aD - \beta D^2/n\right) + \text{KS}(\mathbf{T} - T\_K) \tag{16}$$

where KS is the factor in 1/day that represents the rate of the CR per day.

The authors of [4] have highlighted that BEDs are additive. It means that if radiotherapy is given in multiple phases, then the BED for each phase can be summated to give the total BED.

Actually, the RBEfs are additive, that is, the biological damages increase when number of irradiation phases increase.

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)? DOI: http://dx.doi.org/10.5772/intechopen.92029*

#### *2.1.1 The BED in interrupted treatments*

where *D1 = n1d1* and *D2 = n2d2*

*exp* �*αD*<sup>1</sup> � *βD*<sup>1</sup>

On multiplication of Eq. (10) by �1/α, then

same Eq. (7) but without the dimension *Gy1.5*

where *D1 = EQD2* and *D2 = D = nd,* then

effect of 9.1% of cell survival.

repopulation.

**20**

This derivation does not need creation of the BED.

α/β = 10 Gy for tumors and α/β = 3 Gy for normal tissues.

The cell repopulation (CR) has been introduced in Eq. (3) as

*BED* ¼ *D* 1 þ

*LQS n*ð Þ¼ , *<sup>D</sup> exp* �*α<sup>D</sup>* � *<sup>β</sup>D*<sup>2</sup>

where T is the overall treatment duration. Tk is the time when the cell repopulation starts.

The CR can be introduced in Eq. (2) as

summated to give the total BED.

number of irradiation phases increase.

the Eq. (11) as

�*αD*<sup>1</sup> � *βD*<sup>1</sup>

*Recent Techniques and Applications in Ionizing Radiation Research*

*n*1*d*<sup>1</sup> þ *n*<sup>1</sup>

2 *=n*<sup>1</sup> <sup>¼</sup> *exp* �*αD*<sup>2</sup> � *<sup>β</sup>D*<sup>2</sup>

2

*d*1 2 *α=β*

20*d* 1 þ

*D*<sup>1</sup> þ *D*<sup>1</sup>

*=n*<sup>2</sup> ¼ �*αD*<sup>2</sup> � *βD*<sup>2</sup>

¼ *n*2*d*<sup>2</sup> þ *n*<sup>2</sup>

Substituting n1 = 30, d1 = 2 Gy (D1 = n1d1 = 60 Gy), and n2 = 20, we obtain the

*d* 1*:*5 

From the Eq. (11) one can derive the current equivalent dose in 2-Gy fractions (EQD2) in Gy, that is, the Eq. (14), if one substitutes n1 = n2 and d2 = 2Gy transform

With the introduction of BED in radiotherapy, the radiation biological effects of radiation treatments have been characterized with BED with generic values

While the BED expression, the Eq. (3), has only one parameter, α/β, the LQS(n,D) has two: α and β. Therefore, a tissue with α = 1 Gy�<sup>1</sup> and α/β = 10 Gy that receives 60 Gy in 30 fractions, that is, d = 2 Gy, will have a biological radiation

> *d* ∝*=β*

K is the factor in Gy/day. According to [4], it is the daily BED equivalent of

where KS is the factor in 1/day that represents the rate of the CR per day. The authors of [4] have highlighted that BEDs are additive. It means that if radiotherapy is given in multiple phases, then the BED for each phase can be

Actually, the RBEfs are additive, that is, the biological damages increase when

¼ *D*<sup>2</sup> þ *D*<sup>2</sup>

2*Gy α=β*

2 *=n*<sup>1</sup> (9)

¼ 140 (12)

� K Tð Þ � *TK* (15)

*<sup>=</sup><sup>n</sup>* <sup>þ</sup> KS Tð Þ � *TK* (16)

*=n*<sup>1</sup> (10)

(11)

(13)

2

*d*2 2 *α=β*

*d α=β*

*EQD*2 ¼ *D d*ð Þ þ *α=β =*ð Þ 2*Gy* þ *α=β* (14)

Many of the current works, such as [5–8] related with the interrupted treatment use directly the BED expression or with some modifications that involve elements, like the cell repopulation.

The BED is one of the most current important tools for compensating interrupted radiation treatments, where, as described in [5] three values of BED (original for the initial prescription, applied before the interruption and a new for compensating the interruption) are considered.

#### **2.2 The BED in brachytherapy (BT)**

The BT may be delivered at high, medium, or low dose rates, respectively HDR, MDR, or LDR.

The BED is also expressed as the product of the total physical dose (D) and a dimensionless factor RE as

$$BED = D \ast \text{RE}.\tag{17}$$

Within of the BED expression, they have tried of including other factors affecting the RBEfs, such as cell sublethal damage (SL), cell repair (Rt), and repopulation (Pt). These inclusions are notary in the BT as shown in [9].

The works of [9–11] are strongly based on the BED. Here the factors affecting RBEf are added in the BED expression or included in its dimensionless subpart, the RE. More than 16 equations modifying Eq. (17) have been developed in this work. The Pt effect is considered in the BED expression as:

$$BED = D \ast RE - RCF \tag{18}$$

$$RCF = K \* \left(T - T\_{delay}\right) \tag{19}$$

where T is the overall time, Tdelay is the delay time after the beginning of treatment before the repopulation rate becomes significant, and K is a parameter of this model.

The Rt effect for a continuous low dose rate is considered into RE as a complex expression in [9]. In the same reference, for permanent implant, the decay of the radioactive sources is incorporated in the factor RE of Eq. (17) as

$$RE = \mathbf{1} + \frac{R\mathbf{0}}{\left(\mu + \lambda\right)\left(\mathbf{\dot{v}}\_{\beta}\right)}\tag{20}$$

where R0 is the initial dose rate, and λ is the radionuclide decay constant.

#### **3. The radiation biological effect (RBEf)**

After the first fraction of irradiation to a living tissue region with a dose d, a number of killed and sublethally damaged cells appear. The mean outcomes of the radiation interactions with the cells are probabilistically related as

$$K + \text{SL} + U = \mathbf{1} \,\, (\mathbf{100\%}) \tag{21}$$

$$\mathcal{S} = \mathcal{S}\mathcal{L} + U\tag{22}$$

$$K + \mathbb{S} = \mathbf{1} \,\, (\mathbf{100\%})\tag{23}$$

**Figure 1.**

*Representation of the radiation biological effects (RBFs) defined by cell kill (K) and sublethally damaged cell (SL), and undamaged cell. Abbreviations: dUmin and dUmax: Respectively the lower and upper limit for stochastic region of U; dKmin and dKmax: Respectively the lower and upper limit for stochastic region of K; dminSL and dmaxSL: Respectively the lower and upper limit for stochastic region of SL; dmlSL: Value of d with maximum of SL; MaxproSL: Maximum value of SL.*

$$K = \mathbb{1} - \mathbb{S} \tag{24}$$

• The first fraction generates a mean *nkc* killed cells, *nslc* sublethally damaged

• For the second and successive fractions, the three kinds of cells are analyzed in

• The radiation can interact with a killed cell or a survived cell. If a random number *gnum* is generated, and *gnum < = nkc/NTC*, then the cell is killed, but

• For a killed cell, the simulator will analyze a new cell; but for a sublethally damaged cell, there are two possibilities: the cell is undamaged or sublethally

• For an undamaged cell, if a new gnum < probability for cell kill (K), this cell will die, but if gnum <= (K+ probability for cell sublethal damage), this is

• For a sublethally damaged cell (SLDC) there is a range of damage degree. Two new random numbers gnum1 and gnum2 are generated, and let us define *KSL = max(gnum1;1-gnum1)*. *If gnum2 < =KSL*, the cell will die, but is kept as a SLDC. The previous condition is associated to a major probability of killing

• While the number of fractions increases, nkc increases, and nudc decreases. The nslc can increase or decrease after the second and successive fractions.

• The number of repaired cells is determined after each fraction or during an

• TCP is calculated as ratio of simulations with nkc = NTC and total of them.

• Eq. (22) shows that survived cells involve sublethally damaged and undamaged

Eq. (1) represents cell survival probability, that is, mean value of the ratio of the sublethally damaged cells and total of them, when a determined living tissue characterized with parameters α and α/β is homogenously irradiated with one fraction of dose d. For this reason, this equation can be considered for whatever healthy cell of a determined tissue as probability of becoming in survived cell after irradiation. Given cell kill is a probabilistic complement of cell survival, then cell kill probability

Our computational simulations have not been previously applied by the current Monte Carlo methods. In the radiobiological modeling and simulation field applied

*K q*ð Þ¼ 1 � *LQ S d*ð Þ (25)

cells. The current radiosensitivity studies only report mean values of probability for S that is the sum of probabilities for SL and U, so we have assumed the probability for SL as SL < = S in our radiobiological simulators.

• The radiosensitivity for cell kill (K) is calculated from Eq. (1) as

damaged. This is defined with a new *gnum > nslc/(nslc + nudc)* for a

cells, and *nudc* undamaged cells from the total cells *NTC.*

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)?*

their possible final outcomes in each fraction.

*DOI: http://dx.doi.org/10.5772/intechopen.92029*

is survived.

undamaged cell.

the SLDC.

interruption.

K=1 � LQS(d)

is equal to

**23**

become in a sublethally damaged.

where K is the mean cell kill; SL is the mean cell sublethal damage; U is the mean undamaged cell; and S is the mean cell survival. **Figure 1** is a representation of RBEfs defined by the mean values of the cell kill, sublethally damaged cell, as well undamaged cell. These are the immediate results of first fraction of irradiation with a dose d in a living tissue.

#### **4. The radiobiological computational simulators (RCSs)**

The computational simulations have led to the development of three radiobiological simulators that determine TCP and mean RBEFs in normal tissue for regular/interrupted treatments, as well as one that obtains similar probabilistic distributions to binomial and Poisson ones. The first application is discussed in [12]. The MatLab applications of these simulators are publicly available in the repository of [13].

The TCP has been traditionally obtained from experimental/observational data, complex phenomenological/mechanistic models as shown in [14]. The TCP computational-calculation methodology simulates possible situations of an irradiated tumor, and is based on probabilistic analysis of three possible kinds of cells and their final results during the interactions for a tumor homogeneously irradiated in a fractionated regimen. The cell repair is taken into account as a temporal process during the interfractions.

Given there will be tumor control when tumor cells are all killed by radiation, it allows to determine TCP based on its probabilistic definition in the computational simulations.

In the region with the minimum dose per fraction of a tumor heterogeneously irradiated, there is the highest value of the cell survival shown by Eq. (1); that is, there is the lowest value of probability of cell kill. For this reason, the TCP should be calculated analyzing the results of interactions in this region, and it is not necessary to consider other tumor regions.

For simulating a fractionated/interrupted treatment, it is considered the following:

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)? DOI: http://dx.doi.org/10.5772/intechopen.92029*


Eq. (1) represents cell survival probability, that is, mean value of the ratio of the sublethally damaged cells and total of them, when a determined living tissue characterized with parameters α and α/β is homogenously irradiated with one fraction of dose d. For this reason, this equation can be considered for whatever healthy cell of a determined tissue as probability of becoming in survived cell after irradiation. Given cell kill is a probabilistic complement of cell survival, then cell kill probability is equal to

$$K(q) = \mathbf{1} - LQ \, \mathcal{S}(d) \tag{25}$$

Our computational simulations have not been previously applied by the current Monte Carlo methods. In the radiobiological modeling and simulation field applied

*K* ¼ 1 � *S* (24)

where K is the mean cell kill; SL is the mean cell sublethal damage; U is the mean

*Representation of the radiation biological effects (RBFs) defined by cell kill (K) and sublethally damaged cell (SL), and undamaged cell. Abbreviations: dUmin and dUmax: Respectively the lower and upper limit for stochastic region of U; dKmin and dKmax: Respectively the lower and upper limit for stochastic region of K; dminSL and dmaxSL: Respectively the lower and upper limit for stochastic region of SL; dmlSL: Value of d with*

undamaged cell; and S is the mean cell survival. **Figure 1** is a representation of RBEfs defined by the mean values of the cell kill, sublethally damaged cell, as well undamaged cell. These are the immediate results of first fraction of irradiation with

**4. The radiobiological computational simulators (RCSs)**

The computational simulations have led to the development of three

complex phenomenological/mechanistic models as shown in [14]. The TCP computational-calculation methodology simulates possible situations of an irradiated tumor, and is based on probabilistic analysis of three possible kinds of cells and their final results during the interactions for a tumor homogeneously irradiated in a fractionated regimen. The cell repair is taken into account as a temporal process

radiobiological simulators that determine TCP and mean RBEFs in normal tissue for regular/interrupted treatments, as well as one that obtains similar probabilistic distributions to binomial and Poisson ones. The first application is discussed in [12]. The MatLab applications of these simulators are publicly available in the repository

The TCP has been traditionally obtained from experimental/observational data,

Given there will be tumor control when tumor cells are all killed by radiation, it allows to determine TCP based on its probabilistic definition in the computational

In the region with the minimum dose per fraction of a tumor heterogeneously irradiated, there is the highest value of the cell survival shown by Eq. (1); that is, there is the lowest value of probability of cell kill. For this reason, the TCP should be calculated analyzing the results of interactions in this region, and it is not necessary

For simulating a fractionated/interrupted treatment, it is considered the

a dose d in a living tissue.

*maximum of SL; MaxproSL: Maximum value of SL.*

*Recent Techniques and Applications in Ionizing Radiation Research*

during the interfractions.

to consider other tumor regions.

of [13].

**Figure 1.**

simulations.

following:

**22**

#### *Recent Techniques and Applications in Ionizing Radiation Research*

to radiotherapy, this methodology will represent a big contribution due to one potential innovation being that rather than evaluating TCP by analytically calculating, the TCP is calculated based on its own probabilistic definition.

quantity, is not associated to a real quantity. When you create models for

there is not BED, but RBEf defined by cell kill and sublethal damage.

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)?*

without introducing the BED.

*DOI: http://dx.doi.org/10.5772/intechopen.92029*

**Author details**

USA

**25**

United States

Terman Frometa-Castillo<sup>1</sup>

and Asghar Mesbahi<sup>4</sup>

S=1 � K, where S: cell survival and K: cell kill.

radiation and total of them in the irradiated tissues.

3 Hospital Universitario Virgen Macarena, Spain

\*Address all correspondence to: terman.frometa@gmail.com

4 Tabriz University of Medical Sciences, Iran

provided the original work is properly cited.

establishing relationships among real quantities, you must not use them for creating new metrics, which happened with the LQ S(n,D) formalism and the BED. Really

The radiobiological (RB) simulators show that radiation produces radiation bio-

BED is an unreal quantity, whose introduction in the radiation therapies has transformed the essential quantifications in the interactions of ionizing radiations with living tissues, where these should be quantified with ratios of cells affected by

The parameters used in the RB simulators, such as killed, sublethally damaged, and undamaged cells are strongly associated to fractionated/interrupted treatments, but they have little familiarization compared with the widely used cell survival.

\*, Anil Pyakuryal<sup>2</sup>

1 Oncology Hospital of Santiago de Cuba, 6134 N Oakley Ave Unit 2, Chicago, IL,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Division of Science and Mathematics, University of District of Columbia,

, Amadeo Wals-Zurita<sup>3</sup>

BED is commonly used for isoeffective dose calculations; but one can use Eq. (2), the LQ S(n,D) for this purposes, that is, this usefulness has been possible

logical effects (RBEfs) instead of BED, which is only a mathematical result of processing the exponential part of the linear-quadratic cell survival model for a fractionated treatment, the LQ S(n,D). It will be a big incoherence if we continue using the BED that is not a real physical quantity. The killed and sublethal damaged cells define the RBEfs. The survived cells are complementing of the former, that is,

Contrary to TCP, the normal tissue complication probability (NTCP) calculation does not have easy way for being determined in the RCSs. Therefore, we have suggested assuming similar-Poisson distributions for the NTCPs, and evaluating safety in the radiation treatments with NTCP0 (normal tissue non-complication probability).

#### **4.1 The RCS in radiotherapy**

In [15], authors recognize that BED formula does not take into account altered fractionation, like twice-daily fractionation. The radiobiological simulators do not have the quoted limitation of the BED. Using computational simulations one can simulate any schedule of fractionation.

Example 1. A normal tissue (NT) region that is characterized with α = 0.0683Gy�<sup>1</sup> and α/β = 1.5Gy; for d = 0.1Gy, its radiosensitivity for cell sublethal damage is equal to 1%. As result of simulating this NT region with cell repair equal to 40% and cell density 10<sup>7</sup> cells/cm<sup>3</sup> , in 30 fractions, the mean cell kill is 30% and mean cell sublethal damage is 0.249%.

As external beam radiotherapy, BT is an activity that involves interactions of ionizing radiations with living tissues, which produce RBEfs into these tissues. The specific treatment duration will depend on many different factors, including the required rate of dose delivery and the type, size, and location of the cancer, and is still calculated from prescribed dose.

Although the authors have not developed radiobiological simulators for BT, the methodology of these tools can be extended to this radiation therapy.

#### *4.1.1 The RCS in interrupted treatments*

An interrupted treatment is a fractionated one, where there is a long-time period greater than the normal interfractions. During the interruption, the sublethally damaged cells have a major possibility of being repaired than during the interfractions of a regular treatment.

Nowadays, the interrupted treatment is evaluated with only a radiobiological tool, the BED. The implementation of the RCSs in the interrupted treatments will represent an extension of the new methodology already applied for the regular treatment.

Cell repopulation, like cell repair, is one of the temporal cellular processes, and is related with the tumor growth, so for an interrupted treatment should be compensating with an increase of the field of the radiation beam.

#### **5. Conclusions**

While the derivation of the LQ S(n,D) model for fractionated regimen considers a 100% cell repair, that is, 0% of sublethally damaged cells (SLDCs), radiobiological simulator methodology takes into account the presence of SLDCs, as well as a cell repair <100% during the interfractions. This makes a better real simulation of the process of interaction of ionizing radiation with living tissues.

The BED is a virtual and redundant radiobiological concept because of this being just a processed subpart of the LQ S(n,D) model by means of a mathematical derivation, and its expression does not model neither physical nor biological

*Biologically Effective Dose (BED) or Radiation Biological Effect (RBEf)? DOI: http://dx.doi.org/10.5772/intechopen.92029*

quantity, is not associated to a real quantity. When you create models for establishing relationships among real quantities, you must not use them for creating new metrics, which happened with the LQ S(n,D) formalism and the BED. Really there is not BED, but RBEf defined by cell kill and sublethal damage.

BED is commonly used for isoeffective dose calculations; but one can use Eq. (2), the LQ S(n,D) for this purposes, that is, this usefulness has been possible without introducing the BED.

The radiobiological (RB) simulators show that radiation produces radiation biological effects (RBEfs) instead of BED, which is only a mathematical result of processing the exponential part of the linear-quadratic cell survival model for a fractionated treatment, the LQ S(n,D). It will be a big incoherence if we continue using the BED that is not a real physical quantity. The killed and sublethal damaged cells define the RBEfs. The survived cells are complementing of the former, that is, S=1 � K, where S: cell survival and K: cell kill.

BED is an unreal quantity, whose introduction in the radiation therapies has transformed the essential quantifications in the interactions of ionizing radiations with living tissues, where these should be quantified with ratios of cells affected by radiation and total of them in the irradiated tissues.

The parameters used in the RB simulators, such as killed, sublethally damaged, and undamaged cells are strongly associated to fractionated/interrupted treatments, but they have little familiarization compared with the widely used cell survival.

#### **Author details**

to radiotherapy, this methodology will represent a big contribution due to one potential innovation being that rather than evaluating TCP by analytically calculat-

does not have easy way for being determined in the RCSs. Therefore, we have suggested assuming similar-Poisson distributions for the NTCPs, and evaluating safety in the radiation treatments with NTCP0 (normal tissue non-complication

Contrary to TCP, the normal tissue complication probability (NTCP) calculation

In [15], authors recognize that BED formula does not take into account altered fractionation, like twice-daily fractionation. The radiobiological simulators do not have the quoted limitation of the BED. Using computational simulations one can

α = 0.0683Gy�<sup>1</sup> and α/β = 1.5Gy; for d = 0.1Gy, its radiosensitivity for cell sublethal damage is equal to 1%. As result of simulating this NT region with cell repair equal

As external beam radiotherapy, BT is an activity that involves interactions of ionizing radiations with living tissues, which produce RBEfs into these tissues. The specific treatment duration will depend on many different factors, including the required rate of dose delivery and the type, size, and location of the cancer, and is

Although the authors have not developed radiobiological simulators for BT, the

An interrupted treatment is a fractionated one, where there is a long-time period

Nowadays, the interrupted treatment is evaluated with only a radiobiological tool, the BED. The implementation of the RCSs in the interrupted treatments will represent an extension of the new methodology already applied for the regular

Cell repopulation, like cell repair, is one of the temporal cellular processes, and is related with the tumor growth, so for an interrupted treatment should be compen-

While the derivation of the LQ S(n,D) model for fractionated regimen considers a 100% cell repair, that is, 0% of sublethally damaged cells (SLDCs), radiobiological simulator methodology takes into account the presence of SLDCs, as well as a cell repair <100% during the interfractions. This makes a better real simulation of the

The BED is a virtual and redundant radiobiological concept because of this being

just a processed subpart of the LQ S(n,D) model by means of a mathematical derivation, and its expression does not model neither physical nor biological

greater than the normal interfractions. During the interruption, the sublethally damaged cells have a major possibility of being repaired than during the

, in 30 fractions, the mean cell kill is 30% and

Example 1. A normal tissue (NT) region that is characterized with

cells/cm<sup>3</sup>

methodology of these tools can be extended to this radiation therapy.

sating with an increase of the field of the radiation beam.

process of interaction of ionizing radiation with living tissues.

ing, the TCP is calculated based on its own probabilistic definition.

*Recent Techniques and Applications in Ionizing Radiation Research*

probability).

**4.1 The RCS in radiotherapy**

to 40% and cell density 10<sup>7</sup>

simulate any schedule of fractionation.

mean cell sublethal damage is 0.249%.

still calculated from prescribed dose.

*4.1.1 The RCS in interrupted treatments*

interfractions of a regular treatment.

treatment.

**5. Conclusions**

**24**

Terman Frometa-Castillo<sup>1</sup> \*, Anil Pyakuryal<sup>2</sup> , Amadeo Wals-Zurita<sup>3</sup> and Asghar Mesbahi<sup>4</sup>

1 Oncology Hospital of Santiago de Cuba, 6134 N Oakley Ave Unit 2, Chicago, IL, USA

2 Division of Science and Mathematics, University of District of Columbia, United States

3 Hospital Universitario Virgen Macarena, Spain

4 Tabriz University of Medical Sciences, Iran

\*Address all correspondence to: terman.frometa@gmail.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Fowler JF. A review: The linear quadratic formula and progress in fractionated radiotherapy. The British Journal of Radiology. 1989;**62**:679-675

[2] Fowler JF. 21 years of Biologically Effective Dose. The British Journal of Radiology. 2010;**83**(991):554-568

[3] The Management of Gynecologic Cancers: Radiobiology [Internet] Available from: https://www.astro.org/ uploadedFiles/Main\_Site/Meetings\_ and\_Events/2013\_Spring\_Refresher\_ Course/Meeting\_Program/ RADIOBIOLOGY%20GYN% 20MARPLES.pdf

[4] Jones B, Dale RG, Deehan C, Hopkins KI, Morgan DAL. The role of biologically effective dose (BED) in clinical oncology. Clinical Oncology. 2001;**13**(2):71-81. DOI: 10.1053/ clon.2001.9221

[5] Dale R, Hendry J, Jones B, et al. Practical methods for compensating for missed treatment days in radiotherapy, with particular reference to head and neck schedules. Clinical Oncology (Royal College of Radiologists (Great Britain)). 2002;**14**:215-220

[6] Putora PM, Schmuecking M, Aebersold D, Plasswilm L. Compensability index for compensation radiotherapy after treatment interruptions. Radiation Oncology. 2012;**7**:208

[7] Yusoff AL, Mohamad M, Abdullah R, et al. Journal of Physics: Conference Series. 2016;**694**:10-12

[8] Royal College of Radiologists. The Timely Delivery of Radical Radiotherapy: Guidelines for the Management of Unscheduled Treatment Interruptions. Fourth ed2019

[9] Dale R, Deehan C. Chapter 7 "Brachytherapy", Radiobiological Modelling in Radiation Oncology. Vol. 2007. London, UK: The British Institute of Radiobiology; 2007. p. 113-137

**Chapter 3**

**Abstract**

in Bulgaria

*Dolchinkov Nikolay Todorov*

and analyses and directions for follow-up are made.

radioactive background, radioactive waste

Convention by leading world powers [2–4].

live in and what happens around us.

**1. Introduction**

**27**

**Keywords:** Bulgaria, disclosure systems, population, radiation risks,

The topic of radiation safety is very painful for society. Despite its timeliness, its

Bulgaria is at the forefront of Europe, Asia, and Africa where people, technology, weapons, and smuggling are being deployed. This, along with the increased terrorist activity in Europe and the banging of weapons around Bulgaria, leads to a concern in part of society [5]. We cannot be indifferent to what kind of world we

All of this has led me to make a survey of the population to what extent it is aware of the problems of radiation safety and what each of us should do in the event of a radiation accident in Bulgaria or near Bulgaria which will lead to an increase of the natural radioactive background [6]. The extent to which the public is aware of the procedures and actions to be taken in changing the radioactive situation should

relevance has not diminished over the past 30 years. In order to increase the monitoring of the radioactive situation, the nuclear accidents in Chernobyl in 1986 and in Fukushima in 2011 played a major role [1]. Simultaneously with the use of the atom for peaceful purposes, over the past 2 years, there has been an increase in the development of new and advanced nuclear weapons. Even in recent months, there has been intense talk about ending the operation of the Nuclear Weapons

State of Radiation Protection

In the months of February and March 2017, I conducted a survey among 3 population groups and 392 participants on the state of the systems for monitoring and alerting the population, so the information received is up-to-date. The information received and summarized should not be taken as a constant, since the situation is changing dynamically, both in terms of the political situation in Bulgaria and the region and the intentions of our neighbors in relation to sites that present radiation risks and in terms of meteorological elements that influence possible radioactive contamination. Particularly dynamic is the development of meteorological elements that need to be analyzed very thoroughly in the event of a nuclear accident or incident. The results and consequences of the closure of uranium production and its processing in Bulgaria, as well as the storage of radioactive waste in Bulgaria, are shown. The results of the study are presented, diagrams are presented,

[10] Report of AAPM TG 137. AAPM Recommendations on Dose Prescription and Reporting Methods for Permanent Interstitial Brachytherapy for Prostate Cancer; 2010

[11] Pritz J. Biological Effective Dose (BED) Distribution Matching for Obtaining Brachytherapy Prescription Doses & Dosimetric Optimization for Hybrid Seed Brachytherapy. University of South Florida; 2011. Available from: http://scholarcommons.usf.edu/cgi/vie wcontent.cgi?article=4493&context=etd

[12] Frometa-Castillo T, Pyakuryal A, Piseaux-Aillon R. Simulator of radiation biological effects in tumor in order to determinate the tumor control probability. Informatics in Medicine Unlocked. 2019;**16**. DOI: 10.1016/j. imu.2019.100217

[13] Available from: https://gitlab.com/ tfrometa

[14] Report of AAPM TG-166. The Use and QA of Biologically Related Models for Treatment Planning; 2012

[15] Machtay M, Bae K, Movsas B, et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non–small cell lung carcinoma treated with chemoradiation: An analysis of the radiation therapy oncology group; Int J. International Journal of Radiation Oncology, Biology, Physics. 2012;**82**(1): 425-434. DOI: 10.1016/j.ijrobp.2010. 09.004

#### **Chapter 3**

**References**

[1] Fowler JF. A review: The linear quadratic formula and progress in fractionated radiotherapy. The British Journal of Radiology. 1989;**62**:679-675

*Recent Techniques and Applications in Ionizing Radiation Research*

Modelling in Radiation Oncology. Vol. 2007. London, UK: The British Institute of Radiobiology; 2007.

[10] Report of AAPM TG 137. AAPM Recommendations on Dose Prescription and Reporting Methods for Permanent Interstitial Brachytherapy for Prostate

[11] Pritz J. Biological Effective Dose (BED) Distribution Matching for Obtaining Brachytherapy Prescription Doses & Dosimetric Optimization for Hybrid Seed Brachytherapy. University of South Florida; 2011. Available from: http://scholarcommons.usf.edu/cgi/vie wcontent.cgi?article=4493&context=etd

[12] Frometa-Castillo T, Pyakuryal A, Piseaux-Aillon R. Simulator of radiation biological effects in tumor in order to determinate the tumor control probability. Informatics in Medicine Unlocked. 2019;**16**. DOI: 10.1016/j.

[13] Available from: https://gitlab.com/

[14] Report of AAPM TG-166. The Use and QA of Biologically Related Models

[15] Machtay M, Bae K, Movsas B, et al. Higher biologically effective dose of radiotherapy is associated with

improved outcomes for locally advanced non–small cell lung carcinoma treated with chemoradiation: An analysis of the radiation therapy oncology group; Int J. International Journal of Radiation Oncology, Biology, Physics. 2012;**82**(1): 425-434. DOI: 10.1016/j.ijrobp.2010.

for Treatment Planning; 2012

p. 113-137

Cancer; 2010

imu.2019.100217

tfrometa

09.004

[2] Fowler JF. 21 years of Biologically Effective Dose. The British Journal of Radiology. 2010;**83**(991):554-568

[3] The Management of Gynecologic Cancers: Radiobiology [Internet] Available from: https://www.astro.org/ uploadedFiles/Main\_Site/Meetings\_ and\_Events/2013\_Spring\_Refresher\_

Course/Meeting\_Program/ RADIOBIOLOGY%20GYN%

[4] Jones B, Dale RG, Deehan C, Hopkins KI, Morgan DAL. The role of biologically effective dose (BED) in clinical oncology. Clinical Oncology. 2001;**13**(2):71-81. DOI: 10.1053/

[5] Dale R, Hendry J, Jones B, et al. Practical methods for compensating for missed treatment days in radiotherapy, with particular reference to head and neck schedules. Clinical Oncology (Royal College of Radiologists (Great

Britain)). 2002;**14**:215-220

Oncology. 2012;**7**:208

Series. 2016;**694**:10-12

Timely Delivery of Radical Radiotherapy: Guidelines for the

Interruptions. Fourth ed2019

**26**

[9] Dale R, Deehan C. Chapter 7 "Brachytherapy", Radiobiological

[6] Putora PM, Schmuecking M,

treatment interruptions. Radiation

Aebersold D, Plasswilm L. Compensability index for compensation radiotherapy after

[7] Yusoff AL, Mohamad M, Abdullah R, et al. Journal of Physics: Conference

[8] Royal College of Radiologists. The

Management of Unscheduled Treatment

20MARPLES.pdf

clon.2001.9221

## State of Radiation Protection in Bulgaria

*Dolchinkov Nikolay Todorov*

#### **Abstract**

In the months of February and March 2017, I conducted a survey among 3 population groups and 392 participants on the state of the systems for monitoring and alerting the population, so the information received is up-to-date. The information received and summarized should not be taken as a constant, since the situation is changing dynamically, both in terms of the political situation in Bulgaria and the region and the intentions of our neighbors in relation to sites that present radiation risks and in terms of meteorological elements that influence possible radioactive contamination. Particularly dynamic is the development of meteorological elements that need to be analyzed very thoroughly in the event of a nuclear accident or incident. The results and consequences of the closure of uranium production and its processing in Bulgaria, as well as the storage of radioactive waste in Bulgaria, are shown. The results of the study are presented, diagrams are presented, and analyses and directions for follow-up are made.

**Keywords:** Bulgaria, disclosure systems, population, radiation risks, radioactive background, radioactive waste

#### **1. Introduction**

The topic of radiation safety is very painful for society. Despite its timeliness, its relevance has not diminished over the past 30 years. In order to increase the monitoring of the radioactive situation, the nuclear accidents in Chernobyl in 1986 and in Fukushima in 2011 played a major role [1]. Simultaneously with the use of the atom for peaceful purposes, over the past 2 years, there has been an increase in the development of new and advanced nuclear weapons. Even in recent months, there has been intense talk about ending the operation of the Nuclear Weapons Convention by leading world powers [2–4].

Bulgaria is at the forefront of Europe, Asia, and Africa where people, technology, weapons, and smuggling are being deployed. This, along with the increased terrorist activity in Europe and the banging of weapons around Bulgaria, leads to a concern in part of society [5]. We cannot be indifferent to what kind of world we live in and what happens around us.

All of this has led me to make a survey of the population to what extent it is aware of the problems of radiation safety and what each of us should do in the event of a radiation accident in Bulgaria or near Bulgaria which will lead to an increase of the natural radioactive background [6]. The extent to which the public is aware of the procedures and actions to be taken in changing the radioactive situation should

be increased. As a purpose, I set myself to explore the real state of public awareness and analyze information to identify awareness-raising measures. I segmented the community to get more reliable information to summarize and analyze. In order to achieve the purpose, I set up a questionnaire with specific questions, and I made a preliminary study of the problem [7].

know-how in the field of radiation protection is needed to be able to respond

The questionnaire from this study is attached in this thesis—Appendix. Upon completion of the survey among all categories of learners, the results obtained were edited by me and summarized in a tabular form, which is attached to the dissertation in Annex 17. Based on the summarized data, we can make several

1.The population is not aware of the measures to be taken by the competent state, municipal, and other authorities in the event of a radiological

In responding, respondents with a higher level of education are more interested in the affected aspects of everyday life and are at least partially aware of the problems related to radiation protection, while those with secondary and lower education are ignorant and uninterested in the discussion in the consultation. Hence the fact that the majority of the respondents are not satisfied with the state's policy regarding the actions and measures taken in the

2.There is a very large difference in the responses of the different groups of respondents as to where the greatest danger for radioactive contamination and a possible nuclear accident comes from. Here the trainees and the random respondents give Turkey the greatest danger, while those who are more familiar with the problem have turned their attention to Romania. All

respondents have unanimously indicated that Greece is not a nuclear threat to Bulgaria, while others say Russia, Ukraine, Hungary, the Czech Republic, and Slovenia, but there is no clear potential other subject that would endanger our radiation security. Despite differences of opinion, they are emerging as major potential contributors to radiation pollution in Romania and Turkey. The

case of a radiation accident (**Figure 1**).

opinion given is illustrated in **Figure 2**.

emergency. This potential problem is viewed with disregard and disinterest by the majority of the population, regardless of gender, age, ethnicity, and education. Older people are more concerned about the problem than young

appropriately.

*State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

statements.

people.

**Figure 1.** *Poll results.*

**29**

Based on the studies, aggregation of information, and analysis of results, a questionnaire containing 20 questions was developed. Inquiry included issues covering the overall vision of radioactive background monitoring systems, population disclosure, action by competent authorities and bodies, and their interaction. Together with these basic radiation protection values, the respondents also expressed their opinion on the main factors that could lead to a radiation accident and the manner of distribution of the radioactive particles, isotopes, and rays in terms of the meteorological elements that influence them. The volume of survey questions was chosen so that it could fully cover the research problem from all the relevant points of view, while not being boring for the survey participants. As the number of questions asked increases, there is a danger that the respondents will not pay due attention to the problems raised and those in the second part will not pay due attention [8]. If it goes to the other extreme and there are too few questions, then we will not get enough of the amount of information we need for the analysis and its next lessons.

#### **2. The main part**

The survey was conducted in February and March 2017 so that the information received is current at the time. The resulting and aggregated information should not be considered as a constant because the situation changes dynamically, both in terms of the political situation in the region and the intentions of our neighbors regarding the sites that represent both the radiation risk and the meteorological elements that affect any radioactive contamination [9]. Especially dynamic is the development of meteorological elements, which should be analyzed very thoroughly in the event of a nuclear accident or incident.

The study was conducted in three groups of respondents. The first group consisted of radiation protection and nuclear physics specialists, who have a deeper understanding of the problems, and their opinion has a greater weight. Due to the specificity of the problem, people from different institutions working in this or near area were involved, but considering the research problem, their circle was not large—38 people responded to the survey. In the selection of these specialists, I endeavored to cover a broader range of institutions—Kozloduy NPP, HEI, BAS, Ministry, RNI at the Bulgarian Academy of Sciences, and others. Due to the avoidance of subjective opinion in the survey, employees working or close to the Vasil Levski NMU did not participate.

The second group of people included randomly selected individuals in different age groups and educational qualifications from all over the country. In this category, the respondents that answered were 196 people of different age, gender, and education.

I also made a study among students in the first course at the Vasil Levski NMU, and the results were also processed and analyzed independently. It was attended by 158 trainees who have received initial training in nuclear, chemical, and biological protection and have some basic knowledge of nuclear accidents and their actions. In summarizing the results, the opinions of the three categories of people are considered separately, making only comparisons, but not a general presentation of the problem because these issues are specific and some

#### *State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

be increased. As a purpose, I set myself to explore the real state of public awareness and analyze information to identify awareness-raising measures. I segmented the community to get more reliable information to summarize and analyze. In order to achieve the purpose, I set up a questionnaire with specific questions, and I made a

Based on the studies, aggregation of information, and analysis of results, a questionnaire containing 20 questions was developed. Inquiry included issues covering the overall vision of radioactive background monitoring systems, population disclosure, action by competent authorities and bodies, and their interaction. Together with these basic radiation protection values, the respondents also expressed their opinion on the main factors that could lead to a radiation accident and the manner of distribution of the radioactive particles, isotopes, and rays in terms of the meteorological elements that influence them. The volume of survey questions was chosen so that it could fully cover the research problem from all the relevant points of view, while not being boring for the survey participants. As the number of questions asked increases, there is a danger that the respondents will not pay due attention to the problems raised and those in the second part will not pay due attention [8]. If it goes to the other extreme and there are too few questions, then we will not get enough of the amount of information we need for the analysis

The survey was conducted in February and March 2017 so that the information received is current at the time. The resulting and aggregated information should not be considered as a constant because the situation changes dynamically, both in terms of the political situation in the region and the intentions of our neighbors regarding the sites that represent both the radiation risk and the meteorological elements that affect any radioactive contamination [9]. Especially dynamic is the

development of meteorological elements, which should be analyzed very

The study was conducted in three groups of respondents. The first group consisted of radiation protection and nuclear physics specialists, who have a deeper understanding of the problems, and their opinion has a greater weight. Due to the specificity of the problem, people from different institutions working in this or near area were involved, but considering the research problem, their circle was not large—38 people responded to the survey. In the selection of these specialists, I endeavored to cover a broader range of institutions—Kozloduy NPP, HEI, BAS, Ministry, RNI at the Bulgarian Academy of Sciences, and others. Due to the avoidance of subjective opinion in the survey, employees working or close to the Vasil

The second group of people included randomly selected individuals in different age groups and educational qualifications from all over the country. In this category, the respondents that answered were 196 people of different age, gender,

I also made a study among students in the first course at the Vasil Levski NMU, and the results were also processed and analyzed independently. It was attended by 158 trainees who have received initial training in nuclear, chemical, and biological protection and have some basic knowledge of nuclear accidents and their actions. In summarizing the results, the opinions of the three categories

of people are considered separately, making only comparisons, but not a general presentation of the problem because these issues are specific and some

thoroughly in the event of a nuclear accident or incident.

preliminary study of the problem [7].

*Recent Techniques and Applications in Ionizing Radiation Research*

and its next lessons.

**2. The main part**

Levski NMU did not participate.

and education.

**28**

know-how in the field of radiation protection is needed to be able to respond appropriately.

The questionnaire from this study is attached in this thesis—Appendix. Upon completion of the survey among all categories of learners, the results

obtained were edited by me and summarized in a tabular form, which is attached to the dissertation in Annex 17. Based on the summarized data, we can make several statements.

1.The population is not aware of the measures to be taken by the competent state, municipal, and other authorities in the event of a radiological emergency. This potential problem is viewed with disregard and disinterest by the majority of the population, regardless of gender, age, ethnicity, and education. Older people are more concerned about the problem than young people.

In responding, respondents with a higher level of education are more interested in the affected aspects of everyday life and are at least partially aware of the problems related to radiation protection, while those with secondary and lower education are ignorant and uninterested in the discussion in the consultation. Hence the fact that the majority of the respondents are not satisfied with the state's policy regarding the actions and measures taken in the case of a radiation accident (**Figure 1**).

2.There is a very large difference in the responses of the different groups of respondents as to where the greatest danger for radioactive contamination and a possible nuclear accident comes from. Here the trainees and the random respondents give Turkey the greatest danger, while those who are more familiar with the problem have turned their attention to Romania. All respondents have unanimously indicated that Greece is not a nuclear threat to Bulgaria, while others say Russia, Ukraine, Hungary, the Czech Republic, and Slovenia, but there is no clear potential other subject that would endanger our radiation security. Despite differences of opinion, they are emerging as major potential contributors to radiation pollution in Romania and Turkey. The opinion given is illustrated in **Figure 2**.

**Figure 1.** *Poll results.*

**Figure 2.** *Bulgaria's threat of a radiological emergency.*

When reading the survey data, it is clear that a large part cannot judge whether the sites in Romania are potentially dangerous because of the lack of the

This leads us to the conclusion that a large part of the population in Bulgaria is not familiar with our neighboring countries and we are not interested in enriching the knowledge about our safe living not only in terms of radiation safety but also in terms of other potential dangers and risks. These data can be found in Annex 17, and these statements are also based on these considerations. Although a referendum was recently held in Bulgaria on whether to develop nuclear power by building new capacities in the consultation, I included such a question. The predominant response was to the Belene NPP, with approval of 80% for nuclear and safety specialists, while for the random respondents, the positive response was 54%. Accordingly, the disapproval was highest in the last category which is 46%, and in the experts it was only 20% [11]. With a ready-made one and almost ready-made second reactor, it is most reasonable to install them on the approved site and put into operation and in Bulgaria to regain its dominant position in the energy exporter region; otherwise, in the near future, we may become extremely energy dependent.

5.The number of people familiar with the National Automated System for Continuous Radioactive Background Control and the system for forecasting the spread of radioactive contamination in case of a major nuclear accident of the National Institute of Meteorology and Hydrology is too small. Even among

the people who work in this area and who are gravitating around these

problems, they are not so prepared for information to fulfill their direct duties. In the consultation, a comment was often made that it is not my direct duties

The percentage of people familiar with the systems varied between 2% and 26%, which is a very low percentage. On this basis, a high percentage of people who have responded positively to the effectiveness of these systems cannot be expected. More than half cannot assess the degree of coordination

necessary information.

*State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

*Potential carriers of radiation risk.*

**Figure 4.**

and I do not care.

**31**

**Figure 3.** *Answer a question "what is your opinion about the state of radiation protection in Bulgaria?"*

3.According to the results of the study, the state of radiation protection in Bulgaria has gaps, and the experts give a higher assessment of reality than the other two groups.

The group of learners and people, selected randomly, gives a lower score, as the lack of information influences this. People with higher education also give higher marks than people with secondary and lower education (**Figure 3**) [10].

4.On a detailed examination of the main sites where nuclear facilities are or could be located, there is also a different degree of suspected danger, the most serious of which is reported by all respondents from Turkey, where the specialists give 37% and the other participants give 57–64%. The other possible answers are given in roughly the same range regardless of the type of category. It is quite clear that the Kozloduy NPP is the most reliable nuclear facility in the region and that radioactive contamination is unlikely to occur (**Figure 4**).

*State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

#### **Figure 4.** *Potential carriers of radiation risk.*

When reading the survey data, it is clear that a large part cannot judge whether the sites in Romania are potentially dangerous because of the lack of the necessary information.

This leads us to the conclusion that a large part of the population in Bulgaria is not familiar with our neighboring countries and we are not interested in enriching the knowledge about our safe living not only in terms of radiation safety but also in terms of other potential dangers and risks. These data can be found in Annex 17, and these statements are also based on these considerations.

Although a referendum was recently held in Bulgaria on whether to develop nuclear power by building new capacities in the consultation, I included such a question. The predominant response was to the Belene NPP, with approval of 80% for nuclear and safety specialists, while for the random respondents, the positive response was 54%. Accordingly, the disapproval was highest in the last category which is 46%, and in the experts it was only 20% [11].

With a ready-made one and almost ready-made second reactor, it is most reasonable to install them on the approved site and put into operation and in Bulgaria to regain its dominant position in the energy exporter region; otherwise, in the near future, we may become extremely energy dependent.

5.The number of people familiar with the National Automated System for Continuous Radioactive Background Control and the system for forecasting the spread of radioactive contamination in case of a major nuclear accident of the National Institute of Meteorology and Hydrology is too small. Even among the people who work in this area and who are gravitating around these problems, they are not so prepared for information to fulfill their direct duties. In the consultation, a comment was often made that it is not my direct duties and I do not care.

The percentage of people familiar with the systems varied between 2% and 26%, which is a very low percentage. On this basis, a high percentage of people who have responded positively to the effectiveness of these systems cannot be expected. More than half cannot assess the degree of coordination

3.According to the results of the study, the state of radiation protection in

*Answer a question "what is your opinion about the state of radiation protection in Bulgaria?"*

4.On a detailed examination of the main sites where nuclear facilities are or could be located, there is also a different degree of suspected danger, the most serious of which is reported by all respondents from Turkey, where the specialists give 37% and the other participants give 57–64%. The other possible answers are given in roughly the same range regardless of the type of category. It is quite clear that the Kozloduy NPP is the most reliable nuclear facility in the region and that radioactive contamination is unlikely to occur (**Figure 4**).

other two groups.

**Figure 2.**

**Figure 3.**

**30**

*Bulgaria's threat of a radiological emergency.*

*Recent Techniques and Applications in Ionizing Radiation Research*

Bulgaria has gaps, and the experts give a higher assessment of reality than the

The group of learners and people, selected randomly, gives a lower score, as the lack of information influences this. People with higher education also give higher marks than people with secondary and lower education (**Figure 3**) [10]. between organizations that monitor the radiation situation and manage the activity of managing a situation with increased radioactive background and take measures to reduce and limit the negative impact on people and the environment [6].

The set of responses to the issues of coordination of the responsible authorities and agencies gives us a real picture of the population's interest in the real radiation situation, how it is monitored, and what actions should be taken to reduce the negative impact. In this respect, the competent state authorities must necessarily improve their work among the population and their coordination among themselves. Only in this way would they weigh in their place and raise their authority, and the population would have greater faith in their actions.

Here too, the predominant is "I cannot judge" again, which is indicative of the fact that a large part of even the experts cannot judge the real picture of the state of coordination among the most important authorities in the field of radiation protection. It is imperative that this responsible work is carried out by professionals and that there is no continuous reorganization of structures and people, depending on the political situation. The professional qualities of the employees should be evaluated, not their political orientation. For example, Italy may be given a position where, despite frequent political changes and elections, the Secretary of the Ministry of Foreign Affairs has headed for more than 30 years, and this creates the security of the institution he represents.

**Figure 5** shows the assessment of the coordination between the responsible

Similar is the picture in the assessment of the coordination between the departments, which they announce when changing the radiation situation in the territory of Bulgaria [12]. There is a peculiarity in responding learners—their opinions are almost equally divided between the four responses. The explanation for this is due to the fact that they have recently received training on nuclear, chemical, and biological accidents and catastrophes, have visited the radiation and other protection authorities at the current Directorate of the Ministry of the Interior, and are under the impressions of the specialists working there. In the other two categories, the fourth

answer is very clear, namely, "I cannot judge." This is shown in **Figure 6**.

organizations are all categorical.

*State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

**Figure 6.**

**33**

following summarized suggestions:

the population will receive it.

All inquiries about the need for more and better quality exercises and annual training of staff responsible for monitoring the radiological situation and especially for government, local authorities, and other non-governmental or voluntary

6.The majority of respondents from the second and third groups did not make suggestions, but there are also very reasonable and reasoned ones. Together with the suggestions of the employees in this field, we can bring them to the

• The need for more quality annual exercises of all responsible institutions.

• Improving interaction between follow-up and disclosure organizations.

• To have up-to-date and accessible information on the radiation situation by explaining to the competent authorities and the media where and how

• In the current development of the technique, the publicity should include, in addition to national television and radio and other electronic media and

• Conducting seminars and refreshing effective staff training.

mobile operators, this being legislatively regulated.

radiation monitoring institutions, according to the respondents.

*Coordination between notifying authorities when changing the radiation situation.*

**Figure 5** shows the assessment of the coordination between the responsible radiation monitoring institutions, according to the respondents.

Here too, the predominant is "I cannot judge" again, which is indicative of the fact that a large part of even the experts cannot judge the real picture of the state of coordination among the most important authorities in the field of radiation protection. It is imperative for these important units for the state to become professionals and not to become a continuous rockade of structures and performers, depending on the political situation. For example, Italy may be given a position where, despite frequent political changes and elections, the Secretary of the Ministry of Foreign Affairs has headed for more than 30 years, and this creates the security of the institution he represents.

**Figure 5.** *Coordination between departments that monitor the radiation situation.*

#### **Figure 6.**

between organizations that monitor the radiation situation and manage the activity of managing a situation with increased radioactive background and take measures to reduce and limit the negative impact on people and the

The set of responses to the issues of coordination of the responsible authorities and agencies gives us a real picture of the population's interest in the real radiation situation, how it is monitored, and what actions should be taken to reduce the negative impact. In this respect, the competent state authorities must necessarily

Here too, the predominant is "I cannot judge" again, which is indicative of the fact that a large part of even the experts cannot judge the real picture of the state of

protection. It is imperative that this responsible work is carried out by professionals and that there is no continuous reorganization of structures and people, depending on the political situation. The professional qualities of the employees should be evaluated, not their political orientation. For example, Italy may be given a position

**Figure 5** shows the assessment of the coordination between the responsible

Here too, the predominant is "I cannot judge" again, which is indicative of the fact that a large part of even the experts cannot judge the real picture of the state of

improve their work among the population and their coordination among themselves. Only in this way would they weigh in their place and raise their authority, and the population would have greater faith in their actions.

*Recent Techniques and Applications in Ionizing Radiation Research*

coordination among the most important authorities in the field of radiation

where, despite frequent political changes and elections, the Secretary of the Ministry of Foreign Affairs has headed for more than 30 years, and this creates the

coordination among the most important authorities in the field of radiation protection. It is imperative for these important units for the state to become professionals and not to become a continuous rockade of structures and performers, depending on the political situation. For example, Italy may be given a position where, despite frequent political changes and elections, the Secretary of the Ministry of Foreign Affairs has headed for more than 30 years, and this creates the

radiation monitoring institutions, according to the respondents.

environment [6].

security of the institution he represents.

security of the institution he represents.

*Coordination between departments that monitor the radiation situation.*

**Figure 5.**

**32**

*Coordination between notifying authorities when changing the radiation situation.*

**Figure 5** shows the assessment of the coordination between the responsible radiation monitoring institutions, according to the respondents.

Similar is the picture in the assessment of the coordination between the departments, which they announce when changing the radiation situation in the territory of Bulgaria [12]. There is a peculiarity in responding learners—their opinions are almost equally divided between the four responses. The explanation for this is due to the fact that they have recently received training on nuclear, chemical, and biological accidents and catastrophes, have visited the radiation and other protection authorities at the current Directorate of the Ministry of the Interior, and are under the impressions of the specialists working there. In the other two categories, the fourth answer is very clear, namely, "I cannot judge." This is shown in **Figure 6**.

All inquiries about the need for more and better quality exercises and annual training of staff responsible for monitoring the radiological situation and especially for government, local authorities, and other non-governmental or voluntary organizations are all categorical.

	- The need for more quality annual exercises of all responsible institutions.
	- Improving interaction between follow-up and disclosure organizations.
	- Conducting seminars and refreshing effective staff training.
	- To have up-to-date and accessible information on the radiation situation by explaining to the competent authorities and the media where and how the population will receive it.
	- In the current development of the technique, the publicity should include, in addition to national television and radio and other electronic media and mobile operators, this being legislatively regulated.

• Increase the control points for monitoring the radiation background, taking into account the research and analysis.

**Appendix**

a) very good; b) good; c) satisfactory; d) bad.

*State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

> a) yes; b) no; c) in part; d) I cannot judge.

> a) yes; b) no; c) in part; d) I cannot judge.

a) Turkey; b) Greece; с) Romania;

a) yes; b) no; c) in part; d) I cannot judge.

a) yes; b) no; c) in part; d) I cannot judge.

a) yes; b) no; c) in part; d) I cannot judge.

a) yes; b) no; c) in part; d) I cannot judge.

a) yes; b) no; c) in part; d) I cannot judge. **10. What is your opinion on the Belene project?** a) it must be finished; b) it must not be completed;

**35**

d) Other (please specify).

**Annex No. 1 THE ANALYSIS OF THE STATUS OF RADIATION PROTECTION IN BULGARIA**

**……………………** *name and family, organization* **………………………**

**3. Do state authorities conduct a proper policy to explain the actions of a radiological emergency?**

**6. Do you consider that the NPP "Cherna Voda" in Romania is a safe plant in normal operation?**

**7. Do you consider that the functional base in Deveselo in Romania by the US missile defense system**

**8. Do you think that the escalation of tensions between Ukraine and Russia and the events in the**

**9. Do you believe that Turkey's policy can affect the security of Turkey's nuclear power plants and the**

**4. Which neighboring countries pose a threat in terms of a potential nuclear threat?**

**5. Do you consider that the Kozloduy NPP is a safe plant in normal operation?**

**represents a danger from the point of view of radiation safety?**

**Crimea could pose a threat to our nuclear safety?**

**storage of rockets that can carry nuclear weapons?**

**1. What is your opinion about the state of radiation protection in Bulgaria?**

**2. Is the population aware of the rules for action on a radiation accident?**

### **3. Conclusions**


### **Appendix**

• Increase the control points for monitoring the radiation background,

1.The data from NASCRPF are used by the competent state authorities for preventive measures and for the organization of measures aimed at limiting the impact on human and the environment of radioactive particles, rays, and

2.The lowest radioactive background in Veliko Tarnovo is the lowest.

population itself is low, as shown by the survey data.

changing the radioactive situation.

organizations is broken.

their financial and resource security.

**34**

3.The awareness of both professionals and voluntary formations and the

4. It is necessary to carry out an explanatory work among the population in order to improve its awareness. It is also necessary to carry out exercises for

5.The radiation gamma background of the neighboring atmospheric layer is within the boundary of the country's background values without significant deviations over the last 20 years. Surface water currents and basins are in good radiological state and are controlled by the control bodies of the EEA in accordance with the applicable regulations. As far as the radiation status of the soils is concerned, no values are found above the backgrounds of the periodic

6.A clear program has been developed and implemented in terms of nuclear safety with the participation of all levels of state and local government. A National Strategy for the Safe Management of Spent Nuclear Fuel and Radioactive Waste has been developed, and the necessary control has been introduced on these activities. It is a weakness that changes the position of the bodies involved in this activity, there is an outflow of specialists, and the thread between the state and municipal authorities and the voluntary

7.Government documents were adopted to solve the problems with the consequences of priority liquidated sites of uranium mining and uranium processing. There are still weaknesses and under-reclaimed sites and unsealed

former mines where environmental pollution from leakages and soils containing uranium and other radioactive isotopes may occur.

8.Research shows that specialists responsible for radiation protection at secondary and lower levels are not sufficiently theoretically and practically prepared and the exercises conducted are not effective. It is necessary for these specialists to undergo refresher courses every year for both radiation and accidents and other accidents. This would help to increase their knowledge, skills, and competencies. The management of NASCRGF is carried out professionally, according to the requirements of the international organizations and according to the domestic and international legislation. An extension is needed from the team of specialists working to monitor the radiation background in Bulgaria, as well as improving

and extraordinary measurements made during the last 15 years.

taking into account the research and analysis.

*Recent Techniques and Applications in Ionizing Radiation Research*

**3. Conclusions**

isotopes.

#### **Annex No. 1 THE ANALYSIS OF THE STATUS OF RADIATION PROTECTION IN BULGARIA**

**……………………** *name and family, organization* **………………………**

	- a) very good;
	- b) good;
	- c) satisfactory;
	- d) bad.

#### **2. Is the population aware of the rules for action on a radiation accident?**


#### **3. Do state authorities conduct a proper policy to explain the actions of a radiological emergency?**


#### **4. Which neighboring countries pose a threat in terms of a potential nuclear threat?**


#### **5. Do you consider that the Kozloduy NPP is a safe plant in normal operation?**


#### **6. Do you consider that the NPP "Cherna Voda" in Romania is a safe plant in normal operation?**

	- a) yes;
	- b) no;
	- c) in part;
	- d) I cannot judge.
	- a) yes;
	- b) no;
	- c) in part;
	- d) I cannot judge.
	- a) yes;
	- b) no;
	- c) in part;
	- d) I cannot judge.
	- a) it must be finished;
		- b) it must not be completed;

#### **11. Do you know the National Automated System for Continuous Radiation Background Control (NASCRВС)?**

	- b) no;
	- a) yes;
	- b) no;
	- c) in part;
	- d) I cannot judge.

#### **13. Does our European Radiation Disaster Response System meet our requirements?**

	- a) yes;
	- b) no;
	- c) in part;
	- d) I cannot judge.

#### **15. Is there sufficient coordination between the agencies that monitor the radiation situation?**


#### **16. Is there sufficient coordination between the departments that disclose the population in case of a radiation accident?**


#### **17. Do you think it is necessary to do more and more qualitative exercises for changing the radiation situation?**

	- a) yes;
	- b) no;
	- c) in part;
	- d) I cannot judge.

**Author details**

Russia

**37**

Dolchinkov Nikolay Todorov1,2

*State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

1 "Vasil Levski" National Military University, Veliko Tarnovo, Bulgaria

\*Address all correspondence to: n\_dolchinkov@abv.bg

provided the original work is properly cited.

2 National Research University "Moscow Power Engineering Institute", Moscow,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,


#### **Thanks for your time and responsiveness! Nikolay Dolchinkov, NMU "Vasil Levski".**

*State of Radiation Protection in Bulgaria DOI: http://dx.doi.org/10.5772/intechopen.91893*

**11. Do you know the National Automated System for Continuous Radiation Background Control**

**14. Do you know the system for forecasting the spread of radioactive contamination in the event of a**

**13. Does our European Radiation Disaster Response System meet our requirements?**

*Recent Techniques and Applications in Ionizing Radiation Research*

**major nuclear accident at the National Institute of Meteorology and Hydrology?**

**15. Is there sufficient coordination between the agencies that monitor the radiation situation?**

**16. Is there sufficient coordination between the departments that disclose the population in case of a**

**17. Do you think it is necessary to do more and more qualitative exercises for changing the radiation**

**18. Do you consider that it is necessary to increase the qualification of the radiation protection officers**

**19. Does Bulgarian legislation comply with current European and international legislation in the field of**

**20. What recommendations do you have for radiation monitoring and public disclosure systems?**

**Thanks for your time and responsiveness! Nikolay Dolchinkov, NMU "Vasil Levski".**

**(NASCRВС)?** a) yes; b) no; c) in part; d) I cannot judge. **12. Is NASCRВС efficient for you?** a) yes; b) no; c) in part; d) I cannot judge.

> a) yes; b) no; c) in part; d) I cannot judge.

> a) yes; b) no; c) in part; d) I cannot judge.

> a) yes; b) no; c) in part; d) I cannot judge.

**radiation accident?** a) yes; b) no; c) in part; d) I cannot judge.

> a) yes; b) no; c) in part; d) I cannot judge.

> a) yes; b) no; c) in part; d) I cannot judge.

**radiation protection?** a) yes; b) no; c) in part; d) I cannot judge.

**36**

**in the basic units working on a voluntary basis?**

**situation?**

### **Author details**

Dolchinkov Nikolay Todorov1,2

1 "Vasil Levski" National Military University, Veliko Tarnovo, Bulgaria

2 National Research University "Moscow Power Engineering Institute", Moscow, Russia

\*Address all correspondence to: n\_dolchinkov@abv.bg

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Dolchinkov N. Analysis and optimization of the national automated system for continuous control of the radiation gamma background. In: Third National Congress of Physical Sciences; Sofia; 2016. ISBN: 978-954-580-364-2. Available from: https://www.researchgate. net/publication/313109065

[2] The Council of Ministers, Annual Report NRA. Sofia; 2015

[3] Commission Regulation (EC) No 1609/2000 of 24 July 2000 establishing a list of products excluded from the application of Council Regulation (EEC) No 737/90 on the conditions governing imports of agricultural products originating in third countries following the accident at the Chernobyl nuclear power station, OJ L 185 25.07.2000. p. 27

[4] Communication from the Commission to the Council and the European Parliament. Communication on Nuclear non-Proliferation. Brussels; 2009

[5] Commission Regulation (Euratom) No 302/2005 of 8 February 2005 on the application of Euratom safeguards— Council/Commission statement, OJ L 054 28.02.2005. p. 1

[6] Dolchinkov N. Modernization of monitoring and public notification systems in case of radioactive pollution of the environment in Bulgaria. Scientific and Practical Journal "Global Nuclear Safety". 2017;**3**(24):7-18. Available from: https://www.researchgate.net/ publication/321905753

[7] Dolchinkov N. Investigation of the state of the radiation control systems and the actions of the competent authorities and the population in the event of a change in the radiation background in Bulgaria. In: International Conference Knowledge-Based Organization Subuy,

Romania. Vol. 24, Issue 3. 2018. рp. 38-44

[8] Dolchinkov N, Nichev N. Structure and management of the national automated system for permanent control of the radiation gamma background in Bulgaria. Land Forces Academy Review. Sibiu, Romania: De Gruyter Open. Vol. XXII, No 2(86); 2017. pp. 115-121

[9] Dolchinkov N. Optimization of the systems for monitoring and public disclosure of radioactive contamination of the environment. International Journal Knowledge, Skopie. 2015;**15**(1): 423-431. ISSN 1857-92. Available from: https://www.researchgate.net/ publication/320378173

[10] Dolchinkov N. State of the population disclosure systems in the changing radiation situation in Bulgaria. In: 12th International Scientific and Practical Conference on Environment, Technology, and Resources, Vol. 1. Rēzekne, Latvia; 20–22 June, 2019. pp. 54-58. ISBN: 1691-5402

Section 2

Natural Radioactivity

**39**

[11] Dolchinkov N. Optimization of the systems for monitoring and public disclosure of radioactive contamination of the environment in Bulgaria [Dissertation for acquisition of NSA Doctor]. Veliko Tarnovo: NMU; 2017. Available from: http://nvu.bg/node/ 1895

[12] Dolchinkov N. Historical overview and analysis of national automated system for continuous monitoring of gamma radiation. In: VIII Scientific and Practical Seminar with International Participation "Economic Security of the State and Scientific and Technological Aspects of its Provision", Kyiv; October 21–22, 2016. рp. 220-228. ISBN: 978-966- 7166-38-0

Section 2
