**1. Introduction**

436 Selected Topics in DNA Repair

Špačková N., Berger I., Šponer J. (2000) Nanosecond Molecular Dynamics of Zipper-like

Stokes S.T., Li X., Grubisic A., Ko Y.J., Bowen K.H. (2007) Intrinsic electrophilic properties of

Takata M., Sasaki M.S., Sonoda E., Morrison C., Hashimoto M., Utsumi H., Yamaguchi-Iwai

Thoma F. (2005) Repair of UV lesions in nucleosomes – intrinsic properties and remodeling.

Van Attikum H., Gasser, S.M. (2005) The histone code at DNA breaks: A guide to repair?

Wang C.-R., Nguyen J., Lu Q.-B. (2009) Bond Breaks of Nucleotides by Dissociative Electron

Wang C.-R., Lu Q.-B. (2010) Molecular Mechanism of the DNA Sequence Selectivity of 5-

Wang W. (2007) Emergence of a DNA-damage response network consisting of Fanconi

Weng X., Ren L., Weng L., Huang J., Zhu S., Zhou X., Weng L. (2007) Synthesis and

Yoshioka Y., Kitagawa Y., Takano Y., Yamaguchi K., Nakamura T., Saito I.J. (1999)

Zeng Y., Wang Y. (2007) UVB-induced formation of intrastrand cross-link products of DNA in MCF-7 cells treated with 5-bromo-20-deoxyuridine. *Biochemistry* 46, 8189–8195. Zimbrick J.D., Ward J.F., Myers L.S. Jr. (1969a) Studies on the chemical basis of cellular

Zimbrick J.D., Ward J.F., Myers L.S. Jr. (1969b) Studies on the chemical basis of cellular

anaemia and BRCA proteins. *Nature Reviews Genetics* 8, 735-748.

5-bromo-20-deoxycytidine. *Nucleic Acids Research* 34, 6521–6529.

Transfer of Nonequilibrium Prehydrated Electrons: A New Molecular Mechanism for Reductive DNA Damage. *Journal of the American Chemical Society* 131, 11320-

Halo-2′-Deoxyuridines as Potential Radiosensitizers. *Journal of the American* 

Biological Studies of Inducible DNA Cross-Linking Agents. *Angewandte Chemie* 119,

Experimental and Theoretical Studies on the Selectivity of GGG Triplets toward One-Electron Oxidation in B-Form DNA. *American Chemical Society* 121, 8712-8719. Zeng Y., Wang Y. (2006) Sequence-dependent formation of intrastrand crosslink products

from the UVB irradiation of duplex DNA containing a 5-bromo-20-deoxyuridine or

radiosensitization by 5-bromouracil substitution in DNA. I. Pulse- and steady-state radiolysis of 5-bromouracil and thymine", *International Journal of Radiation Biology*

radiosensitization by 5-bromouracil substitution in DNA. II. Pulse- and steady-state radiolysis of bromouracil-substituted and unsubstituted DNA, *International Journal* 

*American Chemical Society* 122, 7564–7572.

*Nature Reviews Molecular Cell Biology.* 6, 757-765.

*Physics* 127, 084321.

*EMBO Journal* 17, 5497-5508.

*Chemical Society* 132, 14710–14713.

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11322.

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*of Radiation Biology* 16, 524-534.

DNA Duplex Structures Containing Sheared G·A Mismatch Pairs. *Journal of the* 

nucleosides: Photoelectron spectroscopy of their parent anions. *Journal of Chemical* 

Y., Shinohara A., Takeda S. (1998) Homologous recombination and nonhomologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells.

> During their working and living activities, humans are constantly exposed to different environmental genotoxic agents. Biological consequences of the exposure are accumulation of different mutations and DNA damage that can lead to disruption of genetic material. Numerous endogenous genotoxic agents can also cause DNA damage. Loss of normal cell function can cause cell death or can result in different health disorders, including teratogenic and cancerogenic effects (Jeggo & Lavin, 2009). There is an increasing concern about mutagenic and cancerogenic effects of genotoxic agents and their influence on individuals who are exposed to them by accident, or by living/working lifestyle (Au, 1991; Carrano & Natarajan, 1988; Kassie et al., 2000).

> Exposure to ionising radiation, as a well known genotoxic agents (Balasem & Ali, 1991; Erexon et al., 1991; Fenech et al., 1990; He et al., 2000; Jeggo & Lavin, 2009), can leed to different DNA damage, such as oxidative damage, base and sugar modification in DNA, apurinic/apirimidinic places, single/double strand chromosomal breaks, adduct creation, inter/intra DNA cross linking and other types of damage (Hall & Giaccia, 2006). Numerous studies deal with ionising radiation exposure of individuals who are chronically professionally exposed to low doses (Andreassi, 2009; Au, 1991; Carrano & Natarajan, 1988; Kassie et al., 2000). The results showed the increase in chromosomal damage during chronically low dose exposure (Barquinero et al., 1993; Boutcher, 1985; Cardoso et al., 2001; Jha, 1991; Nowak & Jankowski, 1991), but without confirmed relationship between the received dose and the intensity of DNA damage (Bolus, 2001; Coates et al., 2004; Morgan, 2003; Mothersill et al., 2000, 2001; Seymour & Mothersill, 2000). The influence of chronically low dose exposure has been considered mutagenic and cancerogenic (Fachini et al., 2009). Although it is possible to estimate the influence of absorbed dose and the effect on the

The Influence of Individual Genome Sensitivity in DNA Damage Repair

2004; Sasaki et al., 2002).

exposure (Valverde et al., 1999).

Martin et al., 1993; Wojewodzka et al., 1998).

Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation 439

Stecca & Gerber, 1998), changes in gene expression, gene transcription regulation are also related with adaptive response. Mutations in genes involved in DNA repair can cause DNA missrepair, chromosome endings fusion, fusion of unprotected telomere ends and double strand breaks after exposure to ionising radiation (Bailey et al., 2004; Bailey & Goodwin,

The accuracy of any risk assessment, especially low dose exposures, depends on both the resolution of the method, and the baseline data obtained in well-selected controls. Alkaline comet assay (single-cell gel electrophoresis, SCGE) is an easy-to-use, quick and very sensitive method for detecting primary DNA strand breaks, that is, direct DNA damage within single cells (Tice et al., 1990; Collins, 2004) and can be applied to proliferating and non proliferating cells (Kassie et al., 2000) to determine DNA damage as a result of endogenous factors, lifestyle (Hoffman & Speit, 2005), and occupational or environmental

After relaxation, DNA can be seen as a comet during electrophoresis due to strand breaks (Singh, 2000). The advantages of this technique are sensitivity, reproducibility, easy to use, low expences. It is a rapid method and the amount of sample necessary for the analysis is very small. Comet assay enables analysis of any sort of cells, whether it is plant, animal or human origin, no matter are those single cells from the cell culture or from the tissue. Due to the short-time performance of this technique (it is possible to have results after few hours), it has become well accepted in investigation of different genotoxic agents both *in vitro* and *in vivo* conditions (Betti et al., 1994; Kassie et al., 2000; Kruszewski et al., 1998; McKelvey-

In this method, single cells are embedded into so called agarosis sandwich. Cytoplasm and membranic cell structures are lysed with high concentrated EDTA solution (ethylenediaminetetraacetic acid) and detergents, causing total cell DNA to be free. There

Neutral version enables detection of double stranded DNA breaks (Olive et al., 1990). Under alkaline conditions, single stranded breaks, alkaline labile sites (AP, parts of DNA that can break easily in alkaline solutions), DNA-DNA and DNA protein crosslinking can be detected. Alkaline labile sites are apurinic and apirimidinic DNA bases that can break easily when exposed to alkaline conditions (Singh et al., 1988). After alkaline/neutral denaturation, the cells undergo electrophoresis. Concerning the high molecular weight of the entire DNA molecule, DNA can not pass through the agarose pores towards the anode. Only the small, damaged fragments can pass through. During electrophoresis, the velocity of those fragments that are caused by single or double chromosome breaks depends on their molecular weight. The smaller they are, the faster they get (Plappert et al., 1995). After electrophoresis, the slides are stained with fluorescent dye (usually ethidium bromide). Epifluorescent microscope is used for single cells analysing. Undamaged cells have round shape, while damaged one are similar to the shape of the comet. The mostly used parameters of comet assay are the tail length (TL), percentage of DNA in tail (TI) and the tail moment (TM). Tail length (usually expressed in micrometers) is measured from the centre of the comet head till the end of the comet tail (that is the distance of the fragments from the major DNA that have travelled through the gel during electrophoresis). It is proportional with DNA damage and with length of the fragments (Singh et al., 1988; Tice et al., 1990). TI is measured with computer programme for comet assay analysis. The amount of the

are two comet assay protocols, whether alkaline or neutral denaturation is used.

exposed individuals, consequences of continuous low dose exposure are still a great topic of researches.

The medical stuff represents the best investigated group of professionals exposed to low levels of ionising radiation (UNSCEAR, 2000). During their work, all the employees wear dosimeters (film, TLD or electronic ones) that are analysed on monthly bases. In addition, they are under regular medical control.

Duration and the intensity of exposure to low doses of ionising radiation have significantly decreased over the last decades. The results of analysed dosimeters showed that the received doses are significantly below the regulatory threshold of 20 mSv per year, sometimes even under the dosimeters detection abilities (Kubelka et al., 2011).

Persons employed in emergency medical units and nuclear medicine workers are exposed to higher doses and show higher DNA damage than workers in diagnostic radiology departments (Sari-Minodier et al., 2007).

Andreassi et al. (2009) reported higher amount of DNA damage among interventional cardiologists when compared to clinical cardiologists. Epidemiological researches have shown the connection between the amounts of accumulated doses and the risk of tumour developing (Berrington et al., 2001; Maitre et al., 2003; Wang et al., 2002; Yoshinaga et al., 1999). Cardisi et al. (2005) reported the relationship between exposure to low doses of ionising radiation and cancer in study that involved 400 000 nuclear industry workers.

Today's general opinion is that initial event in radiation carcinogenesis is un/ missrepaired double strand break of DNA molecule, which is a major lesion that leads to developing of chromosomal abnormalities and genetic mutations (Little, 2000).

Accidental or therapeutical acute exposure to ionising radiation can cause different cytogenetic damage, including higher amount of micronuclei (small amount of chromatin in the shape of small nuclei in cytoplasm that was not divided into two new nuclei after first cell division) and chromosomal aberrations (single /double strand breaks of chromosome, inter/intra chromosomal exchange, dicentrics, acentrics, etc.). Recently, different biomarkers are used for monitoring of people occupationally exposed to chronical low doses of ionising radiation. The use of combined biomarkers can offer better assessment and health care of those individuals. With them a phenomenon of adaptive response has been observed. This response can be seen after the first adapting dose of ionising radiation is received (mostly under 10 cGy). After exposure to higher, so called challenging dose, above 100 cGy, those individuals show lower amount of DNA damage when compared to those who did not receive the first, adapting dose. There is also evidence that the amount of dose received can influence the adaptive response (Gourabi & Mozdarani, 1998). A great variability in DNA damage response to ionising radiation exposure of cell lines *in vitro* and individuals *in vivo*  have been reported (Bosi & Olivieri, 1989; Shadley & Wiencke, 1989). Adaptive response has been shown also in persons after clinical, environmental or working exposure (Barquinero et al., 1993, 1995, 1996; Monsieurs et al., 2000; Padovani et al., 1995; Szumiel, 1998; Tedeschi et al., 1995, 1996). Individual differences in DNA repair genes can also influence on this response (Milić, 2010).

Molecular mechanisms of adaptive response are still not clear. It has been considered that it depends on the synthesis and/or protein expression, especially those involved in DNA repair mechanism (Boothman et al., 1989; Ikushima, 1989, 1996; Robson et al., 1999; Wolf et al., 1989, 1996; Youngblom et al., 1989). Early induction response (Okayasu et al., 2000;

exposed individuals, consequences of continuous low dose exposure are still a great topic of

The medical stuff represents the best investigated group of professionals exposed to low levels of ionising radiation (UNSCEAR, 2000). During their work, all the employees wear dosimeters (film, TLD or electronic ones) that are analysed on monthly bases. In addition,

Duration and the intensity of exposure to low doses of ionising radiation have significantly decreased over the last decades. The results of analysed dosimeters showed that the received doses are significantly below the regulatory threshold of 20 mSv per year,

Persons employed in emergency medical units and nuclear medicine workers are exposed to higher doses and show higher DNA damage than workers in diagnostic radiology

Andreassi et al. (2009) reported higher amount of DNA damage among interventional cardiologists when compared to clinical cardiologists. Epidemiological researches have shown the connection between the amounts of accumulated doses and the risk of tumour developing (Berrington et al., 2001; Maitre et al., 2003; Wang et al., 2002; Yoshinaga et al., 1999). Cardisi et al. (2005) reported the relationship between exposure to low doses of ionising radiation and

Today's general opinion is that initial event in radiation carcinogenesis is un/ missrepaired double strand break of DNA molecule, which is a major lesion that leads to developing of

Accidental or therapeutical acute exposure to ionising radiation can cause different cytogenetic damage, including higher amount of micronuclei (small amount of chromatin in the shape of small nuclei in cytoplasm that was not divided into two new nuclei after first cell division) and chromosomal aberrations (single /double strand breaks of chromosome, inter/intra chromosomal exchange, dicentrics, acentrics, etc.). Recently, different biomarkers are used for monitoring of people occupationally exposed to chronical low doses of ionising radiation. The use of combined biomarkers can offer better assessment and health care of those individuals. With them a phenomenon of adaptive response has been observed. This response can be seen after the first adapting dose of ionising radiation is received (mostly under 10 cGy). After exposure to higher, so called challenging dose, above 100 cGy, those individuals show lower amount of DNA damage when compared to those who did not receive the first, adapting dose. There is also evidence that the amount of dose received can influence the adaptive response (Gourabi & Mozdarani, 1998). A great variability in DNA damage response to ionising radiation exposure of cell lines *in vitro* and individuals *in vivo*  have been reported (Bosi & Olivieri, 1989; Shadley & Wiencke, 1989). Adaptive response has been shown also in persons after clinical, environmental or working exposure (Barquinero et al., 1993, 1995, 1996; Monsieurs et al., 2000; Padovani et al., 1995; Szumiel, 1998; Tedeschi et al., 1995, 1996). Individual differences in DNA repair genes can also influence on this

Molecular mechanisms of adaptive response are still not clear. It has been considered that it depends on the synthesis and/or protein expression, especially those involved in DNA repair mechanism (Boothman et al., 1989; Ikushima, 1989, 1996; Robson et al., 1999; Wolf et al., 1989, 1996; Youngblom et al., 1989). Early induction response (Okayasu et al., 2000;

sometimes even under the dosimeters detection abilities (Kubelka et al., 2011).

cancer in study that involved 400 000 nuclear industry workers.

chromosomal abnormalities and genetic mutations (Little, 2000).

researches.

they are under regular medical control.

departments (Sari-Minodier et al., 2007).

response (Milić, 2010).

Stecca & Gerber, 1998), changes in gene expression, gene transcription regulation are also related with adaptive response. Mutations in genes involved in DNA repair can cause DNA missrepair, chromosome endings fusion, fusion of unprotected telomere ends and double strand breaks after exposure to ionising radiation (Bailey et al., 2004; Bailey & Goodwin, 2004; Sasaki et al., 2002).

The accuracy of any risk assessment, especially low dose exposures, depends on both the resolution of the method, and the baseline data obtained in well-selected controls. Alkaline comet assay (single-cell gel electrophoresis, SCGE) is an easy-to-use, quick and very sensitive method for detecting primary DNA strand breaks, that is, direct DNA damage within single cells (Tice et al., 1990; Collins, 2004) and can be applied to proliferating and non proliferating cells (Kassie et al., 2000) to determine DNA damage as a result of endogenous factors, lifestyle (Hoffman & Speit, 2005), and occupational or environmental exposure (Valverde et al., 1999).

After relaxation, DNA can be seen as a comet during electrophoresis due to strand breaks (Singh, 2000). The advantages of this technique are sensitivity, reproducibility, easy to use, low expences. It is a rapid method and the amount of sample necessary for the analysis is very small. Comet assay enables analysis of any sort of cells, whether it is plant, animal or human origin, no matter are those single cells from the cell culture or from the tissue. Due to the short-time performance of this technique (it is possible to have results after few hours), it has become well accepted in investigation of different genotoxic agents both *in vitro* and *in vivo* conditions (Betti et al., 1994; Kassie et al., 2000; Kruszewski et al., 1998; McKelvey-Martin et al., 1993; Wojewodzka et al., 1998).

In this method, single cells are embedded into so called agarosis sandwich. Cytoplasm and membranic cell structures are lysed with high concentrated EDTA solution (ethylenediaminetetraacetic acid) and detergents, causing total cell DNA to be free. There are two comet assay protocols, whether alkaline or neutral denaturation is used.

Neutral version enables detection of double stranded DNA breaks (Olive et al., 1990). Under alkaline conditions, single stranded breaks, alkaline labile sites (AP, parts of DNA that can break easily in alkaline solutions), DNA-DNA and DNA protein crosslinking can be detected. Alkaline labile sites are apurinic and apirimidinic DNA bases that can break easily when exposed to alkaline conditions (Singh et al., 1988). After alkaline/neutral denaturation, the cells undergo electrophoresis. Concerning the high molecular weight of the entire DNA molecule, DNA can not pass through the agarose pores towards the anode. Only the small, damaged fragments can pass through. During electrophoresis, the velocity of those fragments that are caused by single or double chromosome breaks depends on their molecular weight. The smaller they are, the faster they get (Plappert et al., 1995). After electrophoresis, the slides are stained with fluorescent dye (usually ethidium bromide). Epifluorescent microscope is used for single cells analysing. Undamaged cells have round shape, while damaged one are similar to the shape of the comet. The mostly used parameters of comet assay are the tail length (TL), percentage of DNA in tail (TI) and the tail moment (TM). Tail length (usually expressed in micrometers) is measured from the centre of the comet head till the end of the comet tail (that is the distance of the fragments from the major DNA that have travelled through the gel during electrophoresis). It is proportional with DNA damage and with length of the fragments (Singh et al., 1988; Tice et al., 1990). TI is measured with computer programme for comet assay analysis. The amount of the

The Influence of Individual Genome Sensitivity in DNA Damage Repair

doses of ionising radiation (Boffetta et al., 1999).

age 40 years, from 23 to 60 years old) (Table 1).

Subjects (No.) F/M

> Age±SD (Min-Max)

Years of exposure±SD

of exposure, smoking status and alcohol consumption.

1999; Winsey et al., 2000).

(Andreassen, 2005).

**2. Materials and methods** 

Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation 441

with decreased DNA repair capacity (Berwick & Vineis, 2000; Chen et al., 2002; Collins & Harrington, 2002; Divine et al., 2001; Hou et al., 2002; Kumar et al., 2003; Sturgis et al.,

The connection between ionising radiation and SNPs in gene involved in DNA repair has been described by several authors (Aka et al., 2004; Hu et al., 2001; Lunn et al., 2000; Touil et al., 2002). There is an increased interest for exploring of SNPs of genes that are part of biological response to ionising radiation and connecting them with clinical sensibility. Those SNPs could be used for an estimation of exposure to ionising radiation

Determination of high risk population on the basis of genetic polymorphism could help in tumour prevention. The influence of polymorphisms can be crucial in the exposure to low

This study included 126 subjects, 70 medical workers occupationally exposed to low doses of ionising radiation (gastroenterologists, cardiologists, anaesthesiologists, surgeons, radiologists, radiology technicians, nurses) of both gender (45 females, 25 men; mean age was 40 years, from 20-60 years old) and 56 individuals in control group who were not exposed to neither ionising radiation nor to chemical mutagens (14 women and men; mean

> 56 14/42

40.53±10.92 (23-60)

Smoking, Y/N 16/40 31/39 Alcohol, Y/N 35/21 21/49

Table 1. Characteristics of the control and exposed group considering the gender, age, years

The examinees were informed of the study scope and experimental details, have filled a standardised questionnaire designed to obtain relevant information on the current health status, medical history, and lifestyle, and gave their written consent, submitted and approved by the local Ethics Committee. The questionnaire included data on the exposure to possible confounding factors: smoking, alcohol consumption, use of medicines, contraceptives, severe infections, or viral diseases over the past six months, vitamin intake, recent vaccinations, presence of known inherited genetic disorders and chronic diseases, family history of cancer, exposure to diagnostic X-rays. Subjects with history of previous radio- or chemotherapy were not included. Exposed group was under regular film

dosimetry and the dose received did not exceed 20mSv/year (data not shown).

(Min-Max) - 12.22±8.65

Control group Exposed group

70 45/25

40.27±10.8 (20-60)

(1-38)

damage is estimated based on the ratio of DNA percentage in head and in tail of a comet. Some researchers prefer tail moment as the most reliable marker of DNA damage, because it combines measurements of tail length and percentage of DNA in tail (Ashby et al., 1995; Hellman et al., 1995; 1997; Mc Kelvey-Martin et al., 1998). Collins (2004) emphasizes the advantage of TI considering that the percentage of the tail DNA reflects the real DNA damage. Comet assay can also detect apoptotic and necrotic cells. Apoptotic cells show small comet head, and most of DNA is spread in tail in the shape of a cloud (Fairbairn et al., 1995; Olive, 1999). Comet assay is also a valuable technique to study the kinetics of primary DNA damage. It enables to estimate the DNA damage level immediately after the exposure, even when the exposure included very small dose in very short exposure period (Tice et al., 1990; Plappert et al., 1995). Fast repair can represent a problem in DNA damage evaluation in populations occupationally exposed to low doses of ionising radiation and therefore the development of sensitive methods is necessary for those experiments. Most of the primary DNA damage is repaired 30 minutes after the exposure to ionising radiation (Frankenberg-Schwager, 1989), and 2 hours after the exposure to dose of 2 Gy, most of the damaged DNA is totally repaired (Plappert et al., 1997).

Polymorphism by definition is expression of different phenotypes in the same species due to the change/s in genotype. They usually include loss (deletion) of small or bigger part of DNA molecule, insertion of specific number of nucleotides or repetition of di-, three-, or oligonucleotides in variant number. The number or repeating differs among individuals.

Variations in human genome are usually caused by variations in DNA sequence, that is based on the change of only one nucleotide (one from the four nucleotides; A-adenine, Tthymine, C-cytosine or G-guanosine is replaced by the other) usually known as SNP polymorphism (*single nucleotide polymorphism*). Among almost 15 million of SNPs in human genome, 50.000 to 100. 000 of them can change the function or gene expression.

The connection of the change in only one nucleotide (that happens once in every 1000nucleotides in human genome) with the complex aetiology of malignant diseases is poorly investigated (Bonassi et al., 2005). More than 7 millions of well known SNPs in human genome appear with the allelic frequency higher than 5% of the entire population (Hinds et al., 2005). More than 70% of SNPs in human population have the frequency less than 5 % and those SNPs are called rare SNPs (Shastry, 2009). The results of new experiments have shown the connection between gene polymorphisms and risk association with disease developing (Norpa, 2004), especially in polymorphisms of DNA repair genes and folic acid metabolism. Polymorphisms can lead to different gene expression (decreased or increased) and through this process can influence on cell repair mechanisms (Hung et al., 2005; Parl, 2005; Weiss et al., 2005; Kotsopoulos et al., 2007). Variations in DNA repair capacity have been also observed among healthy individuals (Setlow, 1983).

Among 130 genes involved in DNA repair mechanisms, 80 of them are carriers of more than 400 SNPs (Mohrenweiser et al., 2003). DNA damage and repair correlate with the radiation sensitivity and are important in radiation protection and radiotherapy (Ross et al., 2000). Due to individual variations, some persons have higher sensitivity when compared with general population (Berwick, 2000). It has been estimated that 10 -15 percent of healthy people have phenotype that shows decreased possibility for successful DNA damage repair (Mohrenweiser & Jones, 1998; Hu et al., 2002a). Higher risk of mutations, genome instability and malignant tumours have been observed among persons with decreased DNA repair capacity (Berwick & Vineis, 2000; Chen et al., 2002; Collins & Harrington, 2002; Divine et al., 2001; Hou et al., 2002; Kumar et al., 2003; Sturgis et al., 1999; Winsey et al., 2000).

The connection between ionising radiation and SNPs in gene involved in DNA repair has been described by several authors (Aka et al., 2004; Hu et al., 2001; Lunn et al., 2000; Touil et al., 2002). There is an increased interest for exploring of SNPs of genes that are part of biological response to ionising radiation and connecting them with clinical sensibility. Those SNPs could be used for an estimation of exposure to ionising radiation (Andreassen, 2005).

Determination of high risk population on the basis of genetic polymorphism could help in tumour prevention. The influence of polymorphisms can be crucial in the exposure to low doses of ionising radiation (Boffetta et al., 1999).
