Abstract

Separation of various mouse spermatogenic cells by the velocity sedimentation technique was used to study the in vitro and in vivo effects of procarbazine on thymidine, uridine and l-leucine incorporation by spermatogonia, early elongated spermatids and late elongated spermatids, respectively. Procarbazine administered i.p. at the maximally tolerated dose (400 mg/kg) resulted in an immediate and prolonged inhibition of thymidine (8% of control), uridine (12-35% of control) and l-leucine (l4-63% of control) uptake into the respective spermatogenic cells during a 30-day Study period. Fertility was assessed by serial mating of mice after procarbazine treatment to determine the correlation between the functional effects and the biochemical action of the drug. The fertility profile indicated that procarbazine affected all spermatogenic cell types with the possible exception of mature spermatozoa and significantly decreased fertility throughout a 55-day period. Correlation coefficients for the percent inhibition of thymidine, uridine and l-leucine uptake vs. the respective drug-induced infertility were 0.99.0.70 and 0.70, respectively, and each was significant. In vitro. studies densonstrated a significant inhibition of thymidine incorporation by spermatogonia and uridine incorporation by early elongated spermatids only when very high concentrations of procarbazine were used. There was no in vitro effect on the utilization of l-leucine by late elongated spermatids at any concentration of procarbazine tested. These in vitro data are compatible with other studies which suggest that procarbazine requires in vito activation. Thus, velocity sedimentation cell separation and serial mating appear to be valuable tools for investigating the biochemical and toxic effects of pharmacological agents on spermatogenesis.