Radio-adaptive responses at a conditioning X-ray dose of 0.45 Gy and a challenging dose of 5.0 Gy on hematopoietic indices were studied in C57BL mice with p53 (Trp53) wild, heterogenous and knockout allele. The conditioning irradiation, given 2 weeks before the challenging irradiation, induced radio-adaptive responses observed as a recovery of the peripheral blood-cell counts of leukocytes, thrombocytes and erythrocytes on day 14 after challenging irradiation in C57BL mice of the wild-type p53(+/+). The pre-irradiation also increased the endogenous spleen colonies (endo-CFU-S) on day 12 and the spleen weight on day 14. On the contrary, the knockout p53(-/-) mice gave no such radio-adaptive response. The heterogenous p53(+/-) mice gave an intermediate response. The radio-adaptive response in hematopoiesis at a challenge dose of 5.0 Gy seems to be a p53-dependent phenomenon. The possible role of induction in radio-resistance through the reduction of p53-drived apoptosis in hematopoietic stem cells in pre-irradiated mice is discussed.

The radioadaptive survival response induced by a conditioning exposure to 0.45 Gy and measured as an increase in 30-day survival after mid-lethal X irradiation was studied in C57BL/6N mice. The acquired radioresistance appeared on day 9 after the conditioning exposure, reached a maximum on days 12-14, and disappeared on day 21. The conditioning exposure 14 days prior to the challenge exposure increased the number of endogenous spleen colonies (CFU-S) on days 12-13 after the exposure to 5 Gy. On day 12 after irradiation, the conditioning exposure also increased the number of endogenous CFU-S to about five times that seen in animals exposed to 4.25-6.75 Gy without preirradiation. The effect of the interval between the preirradiation and the challenge irradiation on the increase in endogenous CFU-S was also examined. A significant increase in endogenous CFU-S was observed when the interval was 14 days, but not 9 days. This result corresponded to the increase in survival observed on day 14 after the challenge irradiation. Radiation-inducted resistance to radiation-induced lethality in mice appears to be closely related to the marked recovery of endogenous CFU-S in the surviving hematopoietic stem cells that acquired radioresistance by preirradiation. Preirradiation enhanced the recovery of the numbers of erythrocytes, leukocytes and thrombocytes very slightly in mice exposed to a sublethal dose of 5 Gy, a dose that does not cause bone marrow death. There appears to be no correlation between the marked increase in endogenous CFU-S and the slight increase or no increase in peripheral blood cells induced by the radioadaptive response. The possible contribution by some factor, such as Il4 or Il11, that has been reported to protect irradiated animals without stimulating hematopoiesis is discussed.

We introduced the hTERT gene into both normal and AT fibroblast cells to establish immortal cells. They are continuously growing beyond 100 PDN. These cells exhibited normal contact inhibition, and their karyotypes were in a diploid range. Induction of p53 and GADD45 proteins by X-ray in normal immortal cells was same as in the corresponding primary cells. In the normal cells, the survival after 5 Gy of high-dose-rate (HDR, 2 Gy/min) irradiation was 0.03, while that after low-dose-rate (LDR, 0.3 mGy/min) irradiation with the same dose was 0.3. However, in AT cells, both HDR and LDR irradiation resulted in the same survival. These results clearly show that the AT cells have a defect in the DNA repair system involved in cellular survival. We also studied induction of the HPRT mutation in normal cells. Mutation frequency after LDR irradiation was 1/8 of the HDR irradiation at the same dose. The mutation-induction after LDR irradiation was dose dependent. 112Small dose pre-irradiation induced radio-resistance and longevity after challenging irradiation in splenectomized C57BL/6 We have reported that pre-irradiation with a small dose (0.3-0.5 Gy) induces radio-resistance (decreased bone marrow death) two weeks later in ICR and C57BL/6 mice. The spleen is well known as an important tissue for hemopoiesis in mice. Spleen dependency for the radio-adaptive response was examined by splenectomy in C57BL/6 mice. The 30-day survival rate after exposure to 6.75 Gy was significantly (p<0.001, Chisquare test) increased by the pre-irradiation, from 43.2% (19/44) to 88.4% (38/43). However, the increment by the pre-irradiation was smaller compared with that in the intact (not splenectomized) animals in the similar conditions. Effect of pre-irradiation on the life span was also examined. The median survival time was 121 (10-166) days for the control and 182 (127-146) days for the pre-irradiated group. The difference of the life span was significant both in generalized Wilcoxon's rank sum test (p=0.0325) and log rank test (p=0.0278). These results indicate that the priming irradiation favors both short-term survival rate shown as 30-day survival rate and long term survival time shown as lifespan in the splenectomized mice. 113FISH examination of blood lymphocytes from Mayak nuclear workers