Interphase action of vinblastine and vincristine: Differences in their lethal action through the mitotic cycle of cultured mammalian cells

Abstract

Abstract Vinblastine and vincristine, agents which cause arrest of cells in mitosis, have been examined for their effect on the survival of synchonously growing HeLa and Chinese hamster cells. At concentrations higher than those sufficient to induce mitotic arrest, both agents were found to exert a differential lethal action depending upon the position of the cells in interphase. Cells exposed for a short time (3 hours) to 0.3 μg/ml of vinblastine are more sensitive in S and in late G 1 than those in other parts of G 1 or in G 2 . Cells exposed to vincristine (0.1 μ/ml) show only the S phase sensitivity. These difference reflect variations in the survival curves for the two drugs in different phases of the cycle. Cells exposed for a short time to lethal doses of either agent during the S phase proceed at a normal rate to mitosis where they are then arrested irreversibly. In addition, vinblastine causes an immediate interphase death by lysis of cells treated in late G 1 .