The effect of dexrazoxane (ICRF-187) on doxorubicin- and daunorubicin-mediated growth inhibition of Chinese hamster ovary cells

Dexrazoxane (ICRF-187) is clinically used to reduce doxorubicin-induced cardiotoxicity. Because dexrazoxane, doxorubicin and daunorubicin all act on DNA topoisomerase II, a study was undertaken to see what effect dexrazoxane had on the growth inhibitory effects of doxorubicin and daunorubicin towards Chinese hamster ovary cells. Dexrazoxane exhibited significant antagonism of doxorubicin- and daunorubicin-mediated growth inhibition when the cells were preincubated with dexrazoxane before the anthracycline was added. Continuous exposure of cells to either anthracycline and low concentrations of dexrazoxane resulted In additive growth inhibitory effects at low anthracycline concentrations, and no effect at higher anthracycline concentrations.