Differential sensitivities of spermatogonial and postspermatogonial cell stages of the mouse to induction of unscheduled DNA synthesis by ethyl- and methyl-nitrosourea

An autoradiographic procedure was used to measure unscheduled DNA synthesis (UDS, DNA repair synthesis) in spermatogonial and postspermatogonial cell stages of mice after treatment with two doses of N-ethyl-N-nitrosourea (ENU ) and N-methyl-N-nitrosourea (MNU). Significant levels of UDS were measured in type A spermatogonia, meiotic spermatocytes, round spermatids, and earl y elongating spermatids but not in mature spermatids. The extent of UDS var ied according to the germ cell stage and the dose. At equimolar concentrati ons, MNU was more efficient than ENU in eliciting a UDS response in all ger m cells. After ENU treatment, type A spermatogonia showed the highest UDS r esponse, while round and elongating spermatids showed the lowest. After MNU treatment, pachytene spermatocytes exhibited the highest UDS response whil e type A spermatogonia showed the lowest. The high UDS response of type A s permatogonia to ENU parallels the well-known high mutational sensitivity of spermatogonia to this chemical. Similarly the high UDS response observed i n meiotic spermatocytes and early spermatid stages after MNU treatment corr elates with the high mutational sensitivity of postspermatogonial stages to MNU. Thus, the present results, like the specific locus mutation studies, indicate that ENU and MNU each has a unique effect on the spermatogenic cel ls. This effect is likely due to the different mechanism of action of ENU a nd MNU at the level of DNA and also to the physiological differences betwee n different germ-cell stages. Teratogenesis Carcinog. Mutagen. 19:339-351, 1999. Published 1999 Wiley-Liss,Inc.