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Effects of Vinblastine on the Proliferative Capacity of L Cells and Their Progress Through the Division Cycle¹

Department of Medical Biophysics, University of Toronto, and The Ontario Cancer Institute, Toronto, Ontario, Canada

L cells in the exponential growth phase in cell culture were exposed to vinblastine sulfate (VLB)³ for various lengths of time and tested for their ability to form macroscopic colonies and to progress through the phases of the cell-division cycle. Concentrations of VLB in the vicinity of 10^-7 gm/ml were found to inhibit the proliferation of L cells and to cause an accumulation of mitotic figures, which reached a maximum after approximately 1 doubling time. The cells in the VLB-treated cultures showed a progressive loss of colony-forming ability; this loss was closely correlated with the accumulation of mitotic figures. When cells were prevented from entering mitosis by the action of a reversible inhibitor of cell proliferation, phenethyl alcohol, they showed no such progressive loss of colony-forming ability in the presence of VLB. Partially synchronized cell populations, in which only cells in late G₁ phase retained colony-forming ability, were tested for their response to VLB. It was found that no loss of colony-forming ability occurred until the cells began to attempt cell division in the presence of VLB. Studies of the time relationships between the various phases of the cycle in VLB-treated cells did not reveal any important retarding effects of VLB on the progress of L cells through the phases of the cell cycle other than mitosis. VLB appears to act primarily on cells at or near mitosis and to cause an irreversible loss of colony-forming ability.

¹ This investigation was supported in part by grants from the National Cancer Institute of Canada, and the USPHS (grant CA-06229-02).

³ The abbreviations used are: VLB, vinblastine sulfate; Tdr-³H, tritiated thymidine; DNA, deoxyribonucleic acid; PEA, phenethyl alcohol; S, DNA synthesis period; G₁, pre-S period; G₂, post-S period; and M, mitosis.

² Research Fellow of the National Cancer Institute of Canada.

Received 3/10/65.