Vinblastine Sulfate: Metaphase Arrest, Inhibition of RNA Synthesis, and Cytotoxicity in Novikoff Rat Hepatoma Cells

Summary

Novikoff rat hepatoma cells (subline N1S1-67) growing in suspension culture were incubated with various concentrations of vinblastine sulfate and analyzed for “cell viability”by vital staining with trypan blue and trypsin sensitivity, for mitotic index, and the capacity to incorporate ³H-uridine into the nucleotide pool and RNA. Treatment with 0.001-0.1 mM vinblastine sulfate caused metaphase arrest without affecting cell viability for at least 8 hours and without significantly inhibiting RNA synthesis for several hours. At higher concentrations (0.2–0.6 mM), vinblastine sulfate caused a concentration-dependent inhibition of the incorporation of ³Huridine into the acid-soluble nucleotide pool and into RNA, and also inhibited the conversion of ribosomal precursor RNA into ribosomal RNA. These inhibitions were probably related to a direct cytotoxic effect, since at these concentrations the drug also caused a dissolution of the nuclei, precipitation of intracellular material, and subsequent cell death; metaphase arrest was not observed.