Spermatogenic stage sensitivity to 6-mercaptopurine in the mouse.

Hybrid (101 X C3H)F1 male mice were given [3H]thymidine intraperitoneally, and 1 h later 150 mg/kg 6-mercaptopurine in 0.03 N NaOH. Autoradiography of testis sections showed that the rate of spermatogenesis was not altered, and the time of appearance of labeled spermatozoa in the ejaculate indicated that 6-mercaptopurine also had no effect on minimum sperm transport time. Labeled spermatozoa persisted in the ejaculate for a longer interval in 6-mercaptopurine-treated males than in controls, most likely as a result of oligospermia. Combined treatment with 150 R X-rays and 150 mg/kg 6-mercaptopurine gave an additive effect and demonstrated conclusively that the peak incidence of dead implants observed at 30.5 - 35.5 days can be attributed to cells treated as preleptotene spermatocytes and must result from genetic damage that is not cytologically detectable; previous work has shown that chromatic and isochromatid breaks at diakinesis-metaphase I occurred only on days 14 and 15 after 150 mg/kg 6-mercaptopurine. From the present experiments it is clear that these aberrations are not related to the dominant lethality at 30.5 - 35.5 days.