EFFECT OF DOXORUBICIN, DAUNORUBICIN, AND IDARUBICIN ON THE GROWTH-RATE OF HUMAN LEUKEMIA-CELLS (K562) STUDIED WITH IMAGE-ANALYSIS

The effects of doxorubicin, daunorubicin, and idarubicin on the growth of K562 cells were investigated by monitoring the formation of indivi dual colonies in semi-solid culture employing an automated image analy sis system. Drug effects were evaluated using short-term exposure (2 h ) at clinically achievable drug plasma concentrations. Following drug exposure, heterogeneity in growth patterns was observed which was cate gorized into three distinct types; (1) continuous growth at a decrease d growth rate; (2) limited growth; (3) no growth. In addition to a con centration-dependent decrease of the growth fraction, a reduction of t he growth rate of the continuously growing colonies was observed. At e quitoxic drug concentrations, comparable changes in growth rate were o bserved for each of the three anthracyclines studied. It is demonstrat ed that the fraction of cells which escape drug-induced growth arrest with therapeutically achievable drug concentrations display a signific ant decrease in growth rate.