EFFECTS OF ETOPOSIDE ON STAGE-SPECIFIC DNA-SYNTHESIS DURING RAT SPERMATOGENESIS

The stage-specific effect of etoposide on spermatogenic DNA synthesis was measured 1, 3 and 18 days after a single intraperitoneal injection of etoposide. Etoposide inhibited premitotic DNA synthesis most effectively at stages II-III and IV-V of the seminiferous epithelial cycle in which DNA synthesis of late spermatogonia takes place. Compared with control levels, DNA synthesis at stages II-III was maximally inhibited 43% and 57% at doses of 5 and 10 mg/kg, respectively, and at stages IV-V the maximal inhibition was 67% and 62%, at doses of 5 and 10 mg/kg respectively. Premeiotic DNA synthesis was not as vulnerable to the etoposide action as premitotic DNA synthesis, the maximal inhibition of premeiotic DNA synthesis was 39% and 41% compared with control at doses of 5 and 10 mg/kg, respectively. Induction of most probably repair-type DNA synthesis was demonstrated in stages I-III, VIIa-b and XII of the cycle. All the effects of etoposide were most apparent 1 and 3 days after treatment but had not totally disappeared 18 days after the treatment.