Ina, Y., Tanooka, H., Yamada, T. and Sakai, K. Suppression of Thymic Lymphoma Induction by Life-Long Low-Dose-Rate Irradiation Accompanied by Immune Activation in C57BL/6 Mice. Radiat. Res. 163, 153–158 (2005). The induction of thymic lymphomas by whole-body X irradiation with four doses of 1.8 Gy (total dose: 7.2 Gy) in C57BL/6 mice was suppressed from a high frequency (90%) to 63% by preirradiation with 0.075 Gy X rays given 6 h before each 1.8-Gy irradiation. This level was further suppressed to 43% by continuous whole-body irradiation with 137 Cs γ rays at a low dose rate of 1.2 mGy/h for 450 days, starting 35 days before the challenging irradiation. Continuous irradiation at 1.2 mGy/h resulting in a total dose of 7.2 Gy over 258 days yielded no thymic lymphomas, indicating that this low-dose-rate radiation does not induce these tumors. Further continuous irradiation up to 450 days (total dose: 12.6 Gy) produced no tumors. Continuously irradiated mice showed no loss of hair and a greater body weight than unirradiated controls. Immune activities of the mice, as measured by the numbers of CD4 + T cells, CD40 + B cells, and antibody-producing cells in the spleen after immunization with sheep red blood cells, were significantly increased by continuous 1.2-mGy/h irradiation alone. These results indicate the presence of an adaptive response in tumor induction, the involvement of radiation-induced immune activation in tumor suppression, and a large dose and dose-rate effectiveness factor (DDREF) for tumor induction with extremely low-dose-rate radiation.

A final series of experiments on tumor induction by repeating <tex-math>${}^{90}{\rm Sr}-{}^{90}{\rm Y}$</tex-math> β irradiation of the back of ICR mice three times weekly throughout the life span showed no tumor incidence with repeated doses of 0.5 Gy per exposure. The whole dose-response relationship for repeated irradiation with 0.5 to 11.8 Gy per exposure, summarized along with data obtained previously, showed a unique nonlinear dose response with saturation of tumor incidence at doses of over 2.5 Gy per exposure and a threshold-like value around 1.5 Gy per exposure.

The backs of female ICR mice were irradiated with β rays from ${}^{90}{\rm Sr}-{}^{90}{\rm Y}$ three times a week throughout life. Previously we observed 100% tumor incidence at five different dose levels ranging from 1.5 to 11.8 Gy per exposure, but no tumor on repeated irradiation with 1.35 Gy for 300 days (Radiat. Res. 115, 488, 1988). In the present study, delay of tumor development was again seen at a dose of 1.5 Gy per exposure, with further delay at 1.0 Gy. The final tumor incidence was 100% with these two doses. At 0.75 Gy per exposure, no tumor appeared within 790 days after the start of irradiation, but one osteosarcoma and one squamous cell carcinoma did finally appear. These findings indicate a threshold-like response of tumor induction in this repeated irradiation system and further suggest that the apparent threshold may be somewhat less than 0.75 Gy per exposure.

Repeated β irradiation of the backs of mice three times a week with radiation doses of 250 to 1180 cGy per exposure induced 100% incidence of tumors. The incidence of skin tumors appeared to be determined by the total number of repeated exposures in this dose range. An abrupt delay in tumor emergence was observed when the radiation dose was reduced from 250 to 150 cGy per exposure, indicating the existence of a critical threshold. Mouse skin resembles human skin rather than rat skin in its response to radiation.

The nature of mutagenic ionizing radiation damage modified by the presence of oxygen or water was examined by comparing mutagenic with lethal expression of the damage in Bacillus subtilis spores irradiated with 6-MeV electrons. No specific difference was recognized between oxygen-dependent and -independent damages or between polA + -dependent and -independent damages with this system. The induced mutation frequency for His + mutation per lethal hit was 4.7 × 10 −5 for all tested cases.

The mutagenic effect of tritiated water was observed with spores of Bacillus subtilis polA strain suspended in 50 mCi/ml of tritiated water for various intervals. Dose rate given by tritium beta particles to spore core was estimated to be 400 rad/hr from some assumptions and E. coli data computed by Bockrath et al. and Sands et al. The initial mutation rate was $4.2\times 10^{-9}$ mutants/rad, as compared with $2.4\times 10^{-9}$ mutants/rad for 60 Co γ rays and $3.3\times 10^{-9}$ mutants/rad for 30-kVp X rays. The mutagenic effect of tritiated water on spores is most likely due to beta particle ionizing radiation damage.

Single- and double-strand breaks of DNA in electron-irradiated Bacillus subtilis spores were measured and compared with those in irradiated vegetative cells by zone sedimentation in alkaline and neutral pH sucrose gradients. DNA in spores was much more resistant to both types of damage than DNA in vegetative cells. Induction of one single-strand break in DNA of spore genome required 2.8 krad compared to 0.13 krad in vegetative cell genome. In other terms, energies of 857 eV in spore DNA and 41 eV in vegetative cell DNA were required to induce one single-strand break, calculated from molecular weights given by weight-average sedimentation distances; or 835 eV and 46 eV, calculated from weight-average molecular weights. The resistance of DNA was maintained after spores were converted to osmotically sensitive spheroplasts; however, the resistance was lost by rupture of the spheroplast structure. This resistance of DNA was not due to the repair activity of spores nor to protective substance in spore coat and cortex. Structural integrity of DNA is considered to be most important in protection of DNA in spores. According to calculations based on the target theory, the idea that one double-strand break in DNA of genome corresponds to one lethal hit seems to be valid in spores and vegetative cells.