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- W2051201030 abstract "Abstract Sublines of P388 leukemia completely resistant to adriamycin (P388/ADR) or daunorubicin (P388/DAU) in vivo were studied in vitro . These sublines were more resistant to the cytotoxic effects of adriamycin (800-fold relative to sensitive parental cell line, P388/S) than to daunorubicin (18-fold for P388/ADR and 56-fold for P388/DAU). When the effects of the drugs on thymidine incorporation were compared in vitro in sensitive and resistant cells, it was observed that slightly higher levels of the drugs were required to inhibit nucleic acid synthesis in the resistant cells. The shift in inhibitory concentration was much less than the shift in cytotoxic concentration, particularly for adriamycin. The uptake and efflux of [G- 3 H]daunorubicin and [14- 14 C]adriamycin were studied. At low concentrations uptake of both drugs was impaired in the resistant sublines, whereas, at high concentrations a difference in uptake between sensitive and resistant cells was not evident. Resistance did not appear to be related to the difference in the rate of uptake. A markedly enhanced efflux of the drugs from the resistant cells was observed which correlated well with the difference in sensitivity of the sublines to adriamycin and daunorubicin. Enhancing the uptake of adriamycin by increasing the pH of the incubation medium and thereby increasing the proportion of non-ionized drug available for diffusion into the cells or by modifiying the cell membrane by the addition of Tween 80 failed to reverse resistance. The binding of daunorubicin to isolated nuclei from P388/S and P388/ADR cells was essentially similar. It is concluded that these anthracycline-resistant cell lines are resistant by virtue of decreased retention of the drugs." @default.
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- W2051201030 date "1978-01-01" @default.
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- W2051201030 title "Uptake and retention of adriamycin and daunorubicin by sensitive and anthracycline-resistant sublines of P388 leukemia" @default.
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- W2051201030 doi "https://doi.org/10.1016/0006-2952(78)90284-8" @default.
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