P53 deficiency produces fewer regenerating spermatogenic tubules after irradiation

Abstract

The survival of clonogenic spermatogonia was assessed by scoring regenerating tubules at 35 days after irradiation, in the p53 null, heterozygote and wild-type mouse. Survival levels in the p53 null mouse after doses between 6 and 16Gy were reduced by a factor of 3-4 compared with the levels in the heterozygote or wild-type mouse, which responded similarly. However the radiosensitivity of the cells was similar in all three types of mice, and was characterised by a D 1.7 Gy. A two-dose experimental pro0 tocol 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 radioresistant clonogenic spermatogonia in the testis of the unirradiated null mouse 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 (D0 3.2 + 0.2 Gy). It is 0 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 stem cell cycle phase distribution resulting in a smaller proportion of resistant stem cells, which are assayed after high doses.