Comparative studies of the uptake of daunorubicin in sensitive and resistant P388 cell lines by flow cytometry and biochemical extraction procedures.

The intracellular accumulation of daunorubicin as determined by flow cytometry correlates well with that as determined by extraction of the drug from cell homogenates. Two P388 mouse leukaemia cell lines showing differential sensitivity to the drug have been used to investigate the transport changes associated with resistance. Resistance to daunorubicin in these cell lines occurs through an alteration in the intracellular accumulation of the drug, resulting from the increased efflux of the anthracycline from the resistant cells. The effect of temperature, drug concentration, pH, and metabolic inhibitors on this process have been investigated. Uptake by a carrier-mediated process of the un-ionised form of the drug (pK = 8.25), coupled with an energy-dependent efflux process, is proposed as the mechanism of cellular accumulation in the case of the resistant cell line.