Induction of unscheduled DNA synthesis in the germ cells of male mice after treatment with hydrazine or procarbazine.
The induction of unscheduled DNA synthesis (UDS) in early spermatid stages of mice was studied after treatment with hydrazine or procarbazine (Natulan). The UDS response was assayed by measuring the levels of [3H]dThd in the nuclei of sperm cells derived from treated and untreated early spermatid stages. The radioactivity present in these nuclei was measured by liquid scintillation counting. Mice were also treated with 100 mg/kg of MMS in order to compare the UDS level induced by this chemical with that induced by hydrazine or procarbazine. The level of UDS induced by hydrazine was not significantly different from that of the untreated controls in any of the 5 doses tested (10-120 mg/kg). Procarbazine, on the contrary, induced UDS in all the 5 doses tested, from 50 to 600 mg/kg. The increase in the UDS response was positively correlated with the increasing dose. The present results with hydrazine indicate either that this compound does not reach the germ cells in sufficient amounts to produce DNA damage or that the repair system in early spermatid stages does not recognize the type of DNA damage produced by this compound. The sensitivity of detection of UDS in the germ cells of male mice is compared with that of the rabbit. At equivalent germ-cell stages and dosage the mouse UDS assay is more sensitive, by a factor of 2 to 3, than the rabbit assay for the induction of UDS by procarbazine and MMS.
D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D006834:Hydrazines / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011344:Procarbazine / Q000633:toxicity*; D013087:Spermatids / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D006834:Hydrazines; C029424:hydrazine; D011344:Procarbazine; D004247:DNA; D013936:Thymidine