IDARUBICIN AND IDARUBICINOL ARE LESS AFFECTED BY TOPOISOMERASE II-RELATED MULTIDRUG-RESISTANCE THAN IS DAUNORUBICIN

We investigated the cytotoxicity and cellular pharmacology of idarubic in (IDA), idarubicinol (IDAol) and daunorubicin (DNR) in K562/VP-H2 ce lls, which show topoisomerase II-related multidrug resistance but do n ot overexpress P-glycoprotein. K562/VP-H2 cells were less resistant to IDA and IDAol than to DNR. There was no significant difference in the accumulation of each drug between K562 and K562/VP-H2 cells. The clea vage of DNA induced by each drug was decreased in K562/VP-H2 cells, ho wever, the decrease in cleavage in K562/VP-H2 cells was less with IDA and IDAol than with DNR. These results suggest that IDA and IDAol have more cytotoxic potency than DNR in topoisomerase II-related multidrug -resistant leukemia cells. (C) 1998 Elsevier Science Ltd. All rights r eserved.