Dose dependence of the cytokinetic and cytotoxic effects of epirubicin in vitro.

CHO cells were exposed in vitro for 1 h to concentrations of 0.1-20 micrograms/ml of the cytostatic drug epirubicin. Population growth, survival fractions, cell-cycle-phase distribution, and BrdU incorporation were analyzed. A fraction of the cells showed a transitory cytostatic reaction at 1 microgram/ml, and greater than 99% of the cells were killed at 10 micrograms/ml. The survival curve was biphasic with a steep slope at concentrations of up to 5 micrograms/ml. Approximately 0.1% of the cells were resistant to higher concentrations of epirubicin. Bivariate DNA/BrdU flow cytometry revealed that the sensitive cells were blocked and probably killed in the G2M phase of the cell cycle.