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• W2021045134 abstract "Uptake, metabolism and binding of tritium-labeled vincristine sulfate were studied in L1210, P388 and P388/VCR murine leukemia cells in vitro. Negligible metabolism of the drug by these cells was suggested by thin-layer chromatography experiments, in which more than 90 per cent of the label was recovered from cells incubated in tritiated vincristine. and greater than 95 per cent of the recovered tritium was found in the vincristine peak. Serial uptake measurements between 30 sec and 40 min disclosed a biphasic uptake pattern, the early component of which demonstrated Michaelis-Menten kinetics, temperature dependence, inhibition by metabolic poisons, and competitive inhibition by the structural analogue, vinblastine. Efflux experiments disclosed a fraction which was not free to leave the cell and progressively increased during uptake, but at a rate slower than that of entry of the alkaloid into the cells. Accumulation of total and of bound vincristine occurred most rapidly in P388 cells, the subline most sensitive among those studied to the cytotoxic effects of vincristine. The results implicate the presence of a carrier-mediated transport mechanism for translocation of the drug into the cells, and suggest that drug resistance in these cells is due at least in part to impaired accumulation and binding of vincristine within the cell." @default.
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• W2021045134 date "1975-03-01" @default.
• W2021045134 modified "2023-09-24" @default.
• W2021045134 title "Uptake and binding of vincristine by murine leukemia cells" @default.
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• W2021045134 doi "https://doi.org/10.1016/0006-2952(75)90185-9" @default.
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