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Differential Activity of Vincristine and Vinblastine against Cultured Cells¹

Cancer Research Group (McEachern Laboratory) [P. J. F., J. R. P., M. S., C. E. C.] and Department of Biochemistry [P. J. F., C. E. C.], University of Alberta, Edmonton, Alberta, Canada T6G 2H7

Vincristine and vinblastine exhibit differential activity against tumors and normal tissues. In this work, a number of cultured cell lines were assayed for their sensitivity to the antiproliferative and cytotoxic effects of the two drugs following short-term (4 hr) or during continuous exposures. Differential activity was not seen when cells were subjected to continuous exposures. The concentrations of vincristine and vinblastine, respectively, that inhibited growth rates by 50% were: mouse leukemia L1210 cells, 4.4 and 4.0 nM; mouse lymphoma S49 cells, 5 and 3.5 nM; mouse neuroblastoma cells, 33 and 15 nM; HeLa cells, 1.4 and 2.6 nM; and human leukemia HL-60 cells, 4.1 and 5.3 nM. In contrast, differential toxicity was seen when cells were subjected to 4-hr exposures and transferred to drug-free medium: the 50% growth-inhibitory concentrations for vincristine and vinblastine, respectively, for inhibition (a) of proliferation of L1210 cells were 100 and 380 nM and of HL-60 cells were 23 and 900 nM and (b) of colony formation of L1210 cells were 6 and >600 nM and of HeLa cells were 33 and 62 nM. Uptake and release of [³H]-vincristine and [³H]vinblastine were examined in L1210 cells under the conditions of growth experiments. Uptake of both drugs was dependent on the pH of culture media, and significantly greater amounts of [³H]vinblastine than of [³H]vincristine were associated with cells after 4-hr exposures to equal concentrations of either drug. When cells were transferred to drug-free medium after 4-hr exposures, vinblastine was released much more rapidly from cells than was vincristine, and by 0.5 hr after resuspension of cells, the amount of vincristine associated with the cells was greater than the amount of vinblastine and remained so for up to at least 6 hr.

¹ Supported by the National Cancer Institute of Canada and the Alberta Heritage Savings Trust Fund: Applied Research—Cancer. Portions of this work were presented in a preliminary report (7).

² Recipient of a Studentship Award from the Alberta Heritage Foundation for Medical Research.

³ To whom requests for reprints should be addressed.

Received 8/22/83. Accepted 5/ 8/84.

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