Calcium modifies the accumulation and retention of daunorubicin by Ehrlich ascites carcinoma

Verapamil restores daunorubicin sensitivity to daunorubicin resistant Ehrlich ascites carcinoma but is without effect when used with daunorubicin in daunorubicin sensitive parental Ehrlich ascites tumor. Energy dependent daunorubicin efflux is more active in drug resistant than in drug sensitive cells. However, daunorubicin retention decreases equivalently in drug resistant and sensitive cells with increasing calcium levels in the presence of both intact and interrupted outward transport. Therefore, (1) daunorubicin accumulation and retention in Ehrlich ascites carcinoma cells is influenced by at least two independent mechanisms and (2) it is likely that verapamil modifies daunorubicin activity in drug resistant tumor variants by mechanisms beyond calcium inhibition.