[Studies of spermatogenic damages induced by anti-cancer agent and anti-androgenic agents in rat testes].
To investigate the mechanisms responsible for and recovery process of spermatogenic damage induced by anti-cancer agent and anti-androgen agents, we experimented with rats injected with those agents. Cis-diamminedichloroplatinum (CDDP) was selected as the anti-cancer agent causing spermatogenic damage. Flutamide and cyproterone acetate were selected as anti-androgen agents. Both of these agents induced histopathological spermatogenic damage. The influences of CDDP on spermatogonia and spermatocytes were remarkable, compared with cyproterone acetate and flutamide, which damaged mainly spermatids. CDDP had severely damaging effects on the DNA-synthesizing activity of spermatogenesis, based on findings using monoclonal antibody proliferating cell nuclear antigen (PCNA), compared with anti-androgen agents. We also studied Sertoli cell function of drug-induced spermatogenic damage in rat testes. Measuring the contents of transferrin in rat testes indicated the damage to Sertoli cell function. High doses of CDDP (8 mg/kg) affected testicular transferrin concentration, but 4 mg/kg and 2 mg/kg of CDDP had no significant effect on Sertoli cell function. Cyproterone acetate and flutamide had severely damaging effects on Sertoli cell function not only at a high dose (30 mg/kg) but at low doses of 15 mg/kg and 7.5 mg/kg. These results showed that an anti-cancer agent primarily affects the DNA synthesizing activity of spermatogonia and spermatocytes, but high doses of these agents also have damaging effect on Sertoli cells, and anti-androgen agents mainly affect Sertoli cells.
Nambu
A
A
Department of Urology, Sapporo Medical University, School of Medicine.
Kumamoto
Y
Y
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D017373:Cyproterone Acetate / Q000633:toxicity; D004261:DNA Replication / Q000187:drug effects; D005485:Flutamide / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology
D000726:Androgen Antagonists; D017373:Cyproterone Acetate; D005485:Flutamide; D002945:Cisplatin