EFFECTS OF VINCRISTINE ON SPERMATOGENESIS STUDIED BY VELOCITY SEDIMENTATION CELL SEPARATION TECHNIQUE AND SERIAL MATING

¹ Laboratory of Toxicology, National Cancer institute, National Institutes of Health, Bethesda, Maryland
² Laboratory of Toxicology, National Cancer institute, National Institutes of health, Bethesda, Maryland

Separation of various mouse spermatogenic cells by the velocity sedimentation technique was used to study the in vitro and in vivo effects of vincristine on thymidine, uridine and l-leucine incorporation by spermatogonia, early elongated spermatids and late elongated spermatids, respectively. Vincristine administered i.p. at the maximally tolerated dose (1.5 mg/kg) resulted in an immediate and prolonged inimibition of thymidine (20-26% of control), uridine (30-60% of control) and l-leucine (20-60% of control) uptake into the respective spermatogenic cells during time 30-day study period. Fertility was assessed by serial mating of mice after vincristine treatment to determine the correlation between the functional effects and the biochemical action of the drug. The fertility profile indicated that vincristine 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, uridline and l-leucine uptake vs. the respective drug-induced infertility were 0.90, 0.72 and 0.89 and each was significant. In vitro effects demonstrated a significant inhibition of thymidine uptake at concentrations as low as 10^-6 M (41% of control). Higher concentrations of vincristine were required to inhibit the cellular incorporation of uridine and l-leucine. Each of these techniques appears to be a valuable method to investigate the biochemical and toxic effects of pharmacological agents on spermatogenesis.