Abstract

PIP: Vincristine, an antitumor alkaloid discovered in 1958, was studied at the National Cancer Institute in Bethesda, Maryland, for its effects on mammalian spermatogenesis. A velocity sedimentation cell separation technique separated the various types of mouse spermatogenic cells. Both in vivo and in vitro effects of vincristine were noted. A single ip administration of 1.5 mg/kg of vincristine inhibited incorporation of thymidine, uridine, and L-leucine by spermatogonia, early elongated spermatids, and late elongated spermatids, respectively. Maximum inhibition of uptake of thymidine and uridine occurred on Days 1-15, while maximum uptake of L-leucine occurred 15 days after the administration. At 24 hours each cell type was directly affected, but prolonged effects most likely reflected maturation of cells damaged early in differentiation. Mating trials showed vincristine induced a prolonged, but reversible, failure of fertility after a single dose of 1.5 mg/kg. The fertility profile indicated all or almost all speramatogenic cell types were affected; however, nondividing spermiogenic cells were apparently more sensitive to vincristine than dividing premeiotic spermatogenic cells. In vitro biochemical data were consistent with the in vivo effects. In vivo trials showed the most pronounced effect to be inhibition of thymidine incorporation. On the other hand, histological studies showed mainly morphologically normal spermatogenic cells.