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Effects of Vincristine on Cell Survival, Cell Cycle Progression, and Mitotic Accumulation in Asynchronously Growing Sarcoma 180 Cells

Section of Cell Kinetics, Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute [H. M., S-S. C., R. G., S. J. O., B. M. C., C. A. S., S. E. S.], and Applied Clinical Engineering Section, Biomedical Engineering and Instrumentation Branch, Division of Research Services [W. H. S.], NIH, Bethesda, Maryland 20205

The effects of vincristine (VCR) on cell survival, cell cycle progression, DNA synthesis, and metaphase accumulation were studied in relation to drug concentration and drug exposure duration in Sarcoma 180 cells in vitro. VCR was found to affect cells in interphase, producing a transient G₂ block at all drug concentrations and drug exposure durations studied. VCR did not affect DNA synthesis directly. Increases in the metaphase index were delayed and always peaked at approximately 8 hr after drug removal, regardless of the duration of drug exposure. Increases in the metaphase index of sufficient magnitude to be commensurate with VCR lethality were observed only with prolonged drug exposure. VCR produced both nuclear fragmentation and polyploidy. The proportion of cells undergoing polyploidy increased progressively with increasing drug exposure duration. Interference with cytokinesis during prolonged VCR exposure may represent a lethal effect of VCR that is separate from its short-term effects. This could serve as the basis for the clinical study of the antitumor effects of prolonged VCR infusions.

¹ To whom requests for reprints should be addressed, at Building 10, Room 12C216, National Cancer Institute, Bethesda, Md. 20205.

Received 10/22/82. Accepted 5/ 5/83.