Effect of different physiological conditions on the action of adriamycin on Chinese hamster cells in vitro

Chronically hypoxic cells were 5 times more resistant to Adriamycin (ADR) than exponentially growing oxic cells. On reoxygenation, resistance decreased slowly to reach the ADR sensitivity of oxic cells after 24 h. With increasing pH, ADR efficiency increased more in oxic than in chronically hypoxic cells. With increasing cell density, ADR efficiency decreased linearly. The differences in ADR efficiency under the various conditions were accompanied by differences in intracellular ADR uptake. Chronically hypoxic cells incorporated 1.6 times less than oxic cells; the incorporation rate at pH 6.5 was half that at pH 7.4; and at a cell density of 5 X 10(5)/bottle the intracellular uptake was 6 times that at 5 X 10(6)/bottle. The observed differences in uptake of ADR were not, however, sufficient to explain the differences in cytotoxicity.