Comparative Cell Killing and Kinetic Effects of Vincristine or Vindesine in Mammalian Cell Lines

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Abstract
Survival curves for several monolayer and suspension cultures following 24-hour exposures to various vincristine (VCR) or vindesine (VDS) concentrations were all of the exponential-plateau type. Cytotoxicity increased with duration of exposure in hamster NIL8 cells and was comparable for both drugs. Murine L5178Y cells, although 200 times more sensitive than NIL8 cells, also showed similar sensitivities to VCR and VDS. Murine neuroblastoma cells proved approximately fivefold less sensitive to VDS than VCR, whereas qualitative and quantitative differences in the activity of these two drugs were noted in human neuroblastoma cells. The lethal effects of VCR and VDS were exerted solely on logarithmically growing NIL8 cells in the S-phase. Plateau-phase human neuroblastoma cells were also significantly less sensitive to both drugs than were logarithmically growing populations, where cell kill occurred during the S-phase. Complete mitotic arrest, induced by a 24-hour exposure to VCR or VDS, was only partially reversible, whereas rapid and complete reversibility occurred after only 5 hours of drug exposure.