Induction of sister-chromatid exchanges by chemotherapeutic drugs in spermatogonia of mice: effects of procarbazine, adriamycin, cyclophosphamide and mitomycin C.
The chemotherapeutic drugs procarbazine (PCB), adriamycin (ADR), cyclophosphamide (CP) and mitomycin C (MMC) were evaluated in vivo for induction of sister-chromatid exchanges (SCEs) in differentiating spermatogonia of mice. There was a dose-dependent increase in SCE induced by the drugs. The lowest doses that enhanced the SCE rate to greater than twice baseline frequency were: 10 (PCB), 0.25 (ADR), 5 (CP) and 0.25 (MMC) mg/kg body weight. Based on the x-fold increase in SCE over baseline frequency, induced by the highest test dose (which permitted analysis of SCE), the drugs evaluated were ranked as follows: CP greater than MMC greater than PCB greater than ADR. The persistence of SCE-inducing lesions in spermatogonia was investigated by giving a treatment of CP (20 mg/kg body weight), 6 and 9 days before completion of 5-bromodeoxyuridine (BrdUrd) administration. Within 6-9 days, the SCE rate returned to the baseline level.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008937:Mitomycins / Q000494:pharmacology; D011344:Procarbazine / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*
D000970:Antineoplastic Agents; D008937:Mitomycins; D011344:Procarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide