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 early elongating spermatids but not in mature spermatids. The extent of UDS varied according to the germ cell stage and the dose. At equimolar concentrations, MNU was more efficient than ENU in eliciting a UDS response in all germ cells. After ENU treatment, type A spermatogonia showed the highest UDS response, while round and elongating spermatids showed the lowest. After MNU treatment, pachytene spermatocytes exhibited the highest UDS response while type A spermatogonia showed the lowest. The high UDS response of type A spermatogonia to ENU parallels the well-known high mutational sensitivity of spermatogonia to this chemical. Similarly, the high UDS response observed in meiotic spermatocytes and early spermatid stages after MNU treatment correlates 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 cells. This effect is likely due to the different mechanism of action of ENU and MNU at the level of DNA and also to the physiological differences between different germ-cell stages. Teratogenesis Carcinog. Mutagen. 19:339-351, 1999. Published 1999 Wiley-Liss, Inc.
Sotomayor
R E
RE
Food and Drug Administration, Center for Food Safety and Applied Nutrition, Division of Toxicological Research, Laurel, Maryland 20708, USA. res@cfsan.fda.gov
Ehling
U H
UH
Sega
G A
GA
D000818:Animals; D001345:Autoradiography; D002453:Cell Cycle / Q000187:drug effects*; D004252:DNA Mutational Analysis; D004260:DNA Repair; D005038:Ethylnitrosourea / Q000494:pharmacology*; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D013093:Spermatogonia / Q000187:drug effects* / Q000378:metabolism
D008770:Methylnitrosourea; D005038:Ethylnitrosourea