Adriamycin uptake, intracellular binding and cytotoxicity in Chinese hamster ovary cells

The interaction between adriamycin influx, efflux and cytotoxicity has been studied in Chinese hamster ovary (CHO) cells. The rate of adriamycin uptake showed no evidence of saturation with increasing concentration suggesting that uptake occurred by passive diffusion. Plateau levels of adriamycin were reached within 20 min and more than 60% of this was firmly bound to the nucleus and did not efflux. Cytotoxicity studies did not correlate with uptake studies in that cell killing was an exponential function of drug exposure time well beyond the point at which intracellular concentrations had reached a maximum. This suggests that bound adriamycin is not primarily responsible for cytotoxicity.