P53 DEFICIENCY PRODUCES FEWER REGENERATING SPERMATOGENIC TUBULES AFTER IRRADIATION

The survival of clonogenic spermatogonia was assessed by scoring regen erating tubules at 35 days after irradiation, in the p53 null, heteroz ygote and wild-type mouse. Survival levels in the p53 null mouse after doses between 6 and 16 Gy were reduced by a factor of 3-4 compared wi th the levels in the heterozygote or wild-type mouse, which responded similarly. However the radiosensitivity of the cells was similar in al l three types of mice, and was characterised by a D-0 = 1.7 Gy. A two- dose experimental protocol was used to show that the reduced level of survival in the null mouse at day 35 after irradiation was compatible with the interpretation that there were fewer functional radioresistan t clonogenic spermatogonia in the testis of the unirradiated null mous e by about a factor of 3 compared with that in the testis of the wild- type. The lower cell number was similar to the number deduced in other mice (BDF1), where the cells were much more resistant (D-0 = 3.2+/-0. 2 Gy). It is concluded that the lack of p53 causes a reduced level of tubule regeneration at 35 days after irradiation. This is probably not due to cellular radiosensitization, but possibly to a change in the s tem cell cycle phase distribution resulting in a smaller proportion of resistant stem cells, which are assayed after high doses.