Unscheduled DNA synthesis in the testis,a secondary test for the evaluation of chemical mutagens

DNA damage induced by methylmethane sulfonate, cyclophosphamide, doxorubicin and procarbazine in male germ cells was assessed in rabbits by the demonstration of unscheduled DNA synthesis (UDS), in meiotic and postmeiotic phases of maturation. Immediately after treatment by the intravenous route tritiated thymidine was injected into both testicles. Subsequently, rabbits were ejaculated serially, sperm heads were isolated and assayed for radioactivity by liquid scintillation counting. Dose-dependent UDS was demonstrated in late spermatocytes and early spermatids. High doses of hycanthone also induced UDS, but isoniazid and metronidazole had no effect. The rabbit testis UDS test takes into account metabolic and pharmacokinetic aspects of the test substances and provides information about their penetration through the blood-testicular barrier. It is therefore useful for secondary evaluation of potential mutagens. UDS induced by procarbazine was abolished by simultaneous treatment with Ara-C. Thus, the test also recognizes substances that inhibit DNA repair synthesis.