**3.4 Effect of antioxidant activity (AOAAAPH)**

Although an effect was observed in the β-glucan administration group, there was no statistically significant difference. The antioxidant activity against peroxy radicals after treatment was subtle.

#### **3.5 Anti-tumor effects**

**Figure 5** shows the measurement of tumor growth rate by β-glucan administration. The doubling time of the non-irradiated group was not different from the doubling time of the control group with respect to the number of days required to double the tumor size and the ratio of the control group to the 6 Gy group. In the local irradiation group (treatment group), the doubling time of the β-glucan +6 Gy group was 1.4 times longer than that of the control group. The doubling time of the β-glucan +6 Gy group did not exceed the doubling time of the 6 Gy group and tended to be slightly shorter. Compared to the 6 Gy group, it was confirmed that tumor growth was suppressed.

#### **4. Discussion**

White blood cells consisting of lymphocytes, granulocytes, and monocytes are deeply involved in immunity. Lymphocytes are roughly classified into T cells and B cells. T cells are associated with cellular immunity, while B cells are associated with humoral immunity through the production of antibodies. T cells are further classified into helper T cells and suppressor T cells, helper T cells play a role in directing and activating B cells, NK cells, killer T cells, cytotoxic T cells, and granulocytes are mediated by blood Phagocytoses vascular walls, bacteria and foreign bodies. Monocytes are transformed into macrophages through morphological changes after moving to tissues, and transmit antigen information to T lymphocytes. In addition, macrophages activate NK and LAK cells. Thus, in white blood cells, lymphocytes distinguish between self and non-self, give instructions, and play a central role in the immune response [15–19]. In this study, in the non-irradiated group, the β-glucan group showed an increase in the number of lymphocytes, suggesting an increase in the overall white blood cell count.

β-Glucan is a mushroom that contains abundant β-(1–3)-D-glucan and β- (1–6)-D-glucan. It has been reported that the number of granulocytes increases in response to Petrchenko et al. Β-(1–3)-D-glucan. Treatment with β-(1–6)-D-glucan has also been reported to cause macrophage activation, increased T cells, and increased TNF-α and IL-release 8 macrophage activation [16–18]. However, intraperitoneal administration of these polysaccharides has also been reported to induce inflammation in the peritoneal cavity due to difficulty in intestinal absorption [20]. Furthermore, β-(1–6)-D-glucan has been reported to accumulate in the liver and spleen after peritoneal and oral administration [21].

This study and previous reports strongly suggest the involvement of β-(1–3)-Dglucan and β-(1–6)-D-glucan. Polysaccharide polysaccharides such as β-(1–3)-Dglucan are difficult to absorb these substances in the peritoneal cavity and intestine and may stimulate intestinal immunity with a slight inflammatory condition. Intestinal mucosal epithelial T lymphocytes are located between intestinal mucosal epithelial cells, and Peyer's patch and lymphoid tissue are located around the digestive tract. The intestine is considered the largest immune system because 70–80% of B lymphocytes are present in the intestinal lymphoid tissue [22–24]. However, with the exception of β-(1–3)-D-glucan, there are few reports that food is directly related to the immune system, regardless of how difficult it is to absorb.

Therefore, this is thought to be due to slight differences in physicochemical structures such as the side chain of β-(1–3)-D-glucan. In addition, β-(1–6)-D-glucan is degraded by beneficial intestinal bacteria and is relatively well absorbed, so it is necessary to consider the relationship with intestinal bacteria [25]. It is therefore speculated that macrophages are activated by the intestinal immune system. IL-8 and TNF-α are released from macrophages, activate helper T cells, and activate the systemic immune system consisting of macrophages, cytotoxic T cells, killer T cells, NK cells, and B cells.

However, there is no good basis for connecting these series of mechanisms and further experimentation is required. Cell damage is the most important side effect of radiation, and lymphocytes are the most sensitive cells [22]. Radiation causes interphase death in the short term [23]. Therefore, the control of radiation effects on lymphocytes essential to the immune system is very important, and the effects on lymphocytes can be viewed as an indicator of radiation-induced cell damage. When the body is exposed to radiation, free radicals such as H •, OH •, and O2 - (superoxide anion) are generated by the decomposition of water molecules by radiation. DNA free radical damage is called an indirect effect. Administration of the redox agent reduced the cytotoxicity induced by O2 produced by ionizing radiation [25].

It has been suggested that the administration of α-glucan, which has a radioprotective effect, does not inhibit the suppression of tumor growth by radiation, but inhibits tumor growth independently [26]. This may be due to low blood flow in hypoxic cells such as tumor cells and low radical scavenger factors in plasma. Therefore, the antitumor components and tumor suppressors of these substances act by activating immune cells [27–30].

In this study, we examined tumor growth of sarcoma 180 alone, but in the future, we will need to explore different types of tumors and adopt more accurate experimental systems.

**Figure 6** shows mechanisms of cell repair in radiation protection.

**Figure 7** shows radiation protection and radical scavenger processes.

**Figure 8** shows the free radical removal mechanism of β-glucan by radiation. *Enterococcus faecalis* is a gram-positive bacterium that belongs to the LAB family. Its cell walls are reported to induce B-cell activation along with stimulation of IgA

**109**

**Figure 7.**

**Figure 6.**

(TCF/LEF) transcriptional activity.

*Radiation protection and radical scavenger processes.*

*New Screening for the Development of Radioprotectors: Radioprotection and Anti-Cancer Effect…*

secretion in the intestine [31], which could remove pathogens from the intestine [32]. To date, several functions of EC-12 have been reported [33, 34]. However, the preventive effects of heat-killed EC-12 on intestinal carcinogenesis have not yet been elucidated. In this study, we demonstrated that administration of heat-killed EC-12 weakly decreased intestinal tumorigenesis in Min mice, Apc-mutant mice that develop many intestinal polyps through activation of β-catenin signaling. Moreover, were vealer that heat-killed EC-12 possesses suppressive function of β-catenin signaling in vitro by measuring T-cell factor/lymphoid enhancer factor

High IFN-γ production as part of the Th1 immune response has been associated with colitis in mice [33]. Furthermore, Ito et al. reported that IFN-γ plays a

*DOI: http://dx.doi.org/10.5772/intechopen.95016*

*Mechanisms of cell repair in radiation protection.*

*New Screening for the Development of Radioprotectors: Radioprotection and Anti-Cancer Effect… DOI: http://dx.doi.org/10.5772/intechopen.95016*

#### **Figure 6.**

*Translational Research in Cancer*

NK cells, and B cells.

and O2

radiation [25].

experimental systems.

spleen after peritoneal and oral administration [21].

to the immune system, regardless of how difficult it is to absorb.

β-Glucan is a mushroom that contains abundant β-(1–3)-D-glucan and β- (1–6)-D-glucan. It has been reported that the number of granulocytes increases in response to Petrchenko et al. Β-(1–3)-D-glucan. Treatment with β-(1–6)-D-glucan has also been reported to cause macrophage activation, increased T cells, and increased TNF-α and IL-release 8 macrophage activation [16–18]. However, intraperitoneal administration of these polysaccharides has also been reported to induce inflammation in the peritoneal cavity due to difficulty in intestinal absorption [20]. Furthermore, β-(1–6)-D-glucan has been reported to accumulate in the liver and

This study and previous reports strongly suggest the involvement of β-(1–3)-Dglucan and β-(1–6)-D-glucan. Polysaccharide polysaccharides such as β-(1–3)-Dglucan are difficult to absorb these substances in the peritoneal cavity and intestine and may stimulate intestinal immunity with a slight inflammatory condition. Intestinal mucosal epithelial T lymphocytes are located between intestinal mucosal epithelial cells, and Peyer's patch and lymphoid tissue are located around the digestive tract. The intestine is considered the largest immune system because 70–80% of B lymphocytes are present in the intestinal lymphoid tissue [22–24]. However, with the exception of β-(1–3)-D-glucan, there are few reports that food is directly related

Therefore, this is thought to be due to slight differences in physicochemical structures such as the side chain of β-(1–3)-D-glucan. In addition, β-(1–6)-D-glucan is degraded by beneficial intestinal bacteria and is relatively well absorbed, so it is necessary to consider the relationship with intestinal bacteria [25]. It is therefore speculated that macrophages are activated by the intestinal immune system. IL-8 and TNF-α are released from macrophages, activate helper T cells, and activate the systemic immune system consisting of macrophages, cytotoxic T cells, killer T cells,

However, there is no good basis for connecting these series of mechanisms and further experimentation is required. Cell damage is the most important side effect of radiation, and lymphocytes are the most sensitive cells [22]. Radiation causes interphase death in the short term [23]. Therefore, the control of radiation effects on lymphocytes essential to the immune system is very important, and the effects on lymphocytes can be viewed as an indicator of radiation-induced cell damage. When the body is exposed to radiation, free radicals such as H •, OH •,


produced by ionizing

by radiation. DNA free radical damage is called an indirect effect. Administration

It has been suggested that the administration of α-glucan, which has a radioprotective effect, does not inhibit the suppression of tumor growth by radiation, but inhibits tumor growth independently [26]. This may be due to low blood flow in hypoxic cells such as tumor cells and low radical scavenger factors in plasma. Therefore, the antitumor components and tumor suppressors of these substances

In this study, we examined tumor growth of sarcoma 180 alone, but in the future, we will need to explore different types of tumors and adopt more accurate

**Figure 8** shows the free radical removal mechanism of β-glucan by radiation. *Enterococcus faecalis* is a gram-positive bacterium that belongs to the LAB family. Its cell walls are reported to induce B-cell activation along with stimulation of IgA

**Figure 6** shows mechanisms of cell repair in radiation protection. **Figure 7** shows radiation protection and radical scavenger processes.

of the redox agent reduced the cytotoxicity induced by O2

act by activating immune cells [27–30].

**108**

*Mechanisms of cell repair in radiation protection.*

**Figure 7.** *Radiation protection and radical scavenger processes.*

secretion in the intestine [31], which could remove pathogens from the intestine [32]. To date, several functions of EC-12 have been reported [33, 34]. However, the preventive effects of heat-killed EC-12 on intestinal carcinogenesis have not yet been elucidated. In this study, we demonstrated that administration of heat-killed EC-12 weakly decreased intestinal tumorigenesis in Min mice, Apc-mutant mice that develop many intestinal polyps through activation of β-catenin signaling. Moreover, were vealer that heat-killed EC-12 possesses suppressive function of β-catenin signaling in vitro by measuring T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity.

High IFN-γ production as part of the Th1 immune response has been associated with colitis in mice [33]. Furthermore, Ito et al. reported that IFN-γ plays a

**Figure 8.** *The free radical removal mechanism of* β*-glucan by radiation.*

fundamental role in the development of colitis in mice [34]. In addition, IFN-γ activates downstream effector cells to produce inflammatory cytokines such as IL-1β. Therefore, suppression of IFN-γ and IL-1β induction may explain the antiinflammatory properties observed with EF-2001. In addition, Th1 or humoral responses are important for resistance to extracellular pathogens and these cells produce certain IL family cytokines, including IL-1β, IL-6, and IL-10 [35–37].
