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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cell cycle dependent uptake and release of anthracycline by drug-resistant and drug-sensitive human leukaemic K562 cells.

The appearance of cellular resistance to antitumor drugs is a major problem in cancer chemotherapy. This results from the overexpression of the mdr 1 gene which encodes the 170 kDa P-glycoprotein or multidrug transporter. The uptake and release of 4'-O-tetrahydropyranyladriamycin by drug-sensitive and drug-resistant K562 cells in the different phase of the cycle have been determined. Synchronized cells were obtained by centrifugal elutriation. The kinetics, as well as the amount of drug intercalated inside the nucleus and free in the cytoplasm, have been determined using a spectrofluorometric method that we have developed and that does not compromise cell viability. The kinetics of active efflux of the drug under the effect of P-glycoprotein has been determined. We have calculated that the number of 4'-O-tetrahydropyranyladriamycin molecules, which are actively effluxed per cell and per second, is constant whatever the cell cycle phase.[1]


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