Accumulation and release of vinblastine and vincristine by HeLa cells: light microscopic, cinematographic, and biochemical study.

The effect of vinblastine (VLB) and vincristine (VCR) on the survival and proliferation of HeLa cells has been studied during continuous and after 3-hr incubations using cell counting and time lapse cinematography. VLB and VCR are accumulated in the cells during drug exposure as shown with 3H-labeled drugs. The intracellular drug concentration after a 3-hr incubation with therapeutic doses (VLB, 0.1 micrograms/ml, or VCR, 0.03 micrograms/ml) and thorough drug removal is 150 to 500 times higher than that in the incubation medium. Both drugs are released from the cells upon restoration to alkaloid-free medium reaching concentrations that are lethal to the cells during continuous incubation. There is, however, a difference in the release of the two drugs. VLB is quickly and readily released from the cells while the release of VCR occurs slowly, since VCR is tenaciously retained by the cells. Both drugs are released predominantly from living cells.