Flow cytometry studies of intracellular adriamycin in single cells in vitro.

Flow cytometry techniques were used to quantify the intracellular fluorescence of Adriamycin in living cells. Additionally, fluorescence-activated cell sorting was utilized to investigate the relationship between intracellular drug concentration and cell viability. Uptake of Adriamycin in cultured cells was found to be highly dependent upon the method of cell growth (e.g., suspension versus monolayer cultures) and on cell density or cell crowding. With constant exposure conditions, however, direct proportionality was observed between mean cellular fluorescence and external Adriamycin concentration. Total cellular fluorescence was found to increase more rapidly than nuclear fluorescence, although both reached an apparent equilibrium in several hr. Under well-controlled exposure conditions, mean cell survival correlated well with mean cellular Adriamycin fluorescence. Similar results were observed for Adriamycin effects on DNA synthesis. Considerable heterogeneity of cellular Adriamycin levels was, however, observed in all cell populations, and fluorescence-activated cell sorting indicated that the cells with the least intracellular Adriamycin did indeed survive best.