Trichlormethine hydrochloride and correlation of its mutagenic and toxic effects on male germ cells in mice

Abstract

The genetic effect of the cytostatic trichlormethine hydrochloride (TS-160 Spofa) was assessed after a 1-week administration using the dominant lethal mutation test (DLM) and the sperm abnormality test. The dosage was 0.5 mg/kg for 7 consecutive days, an equivalent of the human therapeutic dosage. Simultaneously, the cytostatic's direct toxic effect on male sex organs was assessed. TS-160 carries a genetic risk for the postmeiotic stages of spermatogenesis (DLM) and is responsible for interference in the morphology of sperm heads through its action on spermatocytes. The toxic effects of TS-160 were found to influence the body weight of mice (days 4–25 after administration), to reduce the relative weight of the testes (days 18–25 after administration), to damage spermatogenesis in the seminiferous tubules (spermatids), to be responsible for an appearance of multinucleate cells in the epididymides, and for an increased rate of abnormality of the heads of fully mature spermatozoa. Our findings stress the need to separate the cytotoxic effects from genetic effects so as to avoid false positives, especially in the test for head abnormalities, and also in the assessment of the fertility of male animals or fertilization of females mated with treated males.