Action of N-isopropyl-?-(2-methylhydrazino)-p-toluamide hydrochloride (procarbazine hydrochloride) in the germ tissue of mice: dominant lethal effects

Abstract

A study was carried out on the effects of N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide (procarbazine, Natulan) in the dominant lethal test in the mouse. Male mice were dosed once and mated with fresh virgin females each week. The utilization of sperm, treated as spermatids or testicular sperm with 100-800 mg/kg, resulted in significant post- and pre-implantation death of embryos. Fertility was markedly reduced after the injection of 200 mg/kg of procarbazine and over. This is probably due to a cell killing effect, the most sensitive stages being differentiating spermatogonia, type A sermatogonia and resting primary spermatocytes. Total sterility was induced for several weeks with doses of 600 and 800 mg/kg. Up to 12 weeks after treatment the number of females with implants was still significantly lower than controls indicating a severe depletion of spermatogonial cells. The spectrum of effects correlates well with the drug's effect on nucleic acid and protein synthesis.

Effect of procarbazine on sperm morphology in syrian hamsters

“…The drug is primarily used in the treatment of hodgkin's disease, bronchial carcinoma, and malignant myeloma (Spivack, 1974). The compound is of special interest because it is negative in the Salmonella/microsome test (McCann et al, 1975) but positive in various mammalian systems for mutagenicity (Ehling and Neuhauser, 1977;Roberts et al, 1979;Wild, 1978), and produces sperm abnormalities in mice . Furthermore, it has been shown that procarbazine disrupts spermatogenesis by arresting germcell populations, thereby causing the cellular associations within the seminiferous epithelium to become asynchronous (Russell et al, 1983).…”