TRANSPORT MECHANISM OF ANTHRACYCLINE DERIVATIVES IN HUMAN LEUKEMIA-CELL LINES - UPTAKE AND EFFLUX OF DAUNORUBICIN AND DOXORUBICIN IN HL-60 AND ITS RESISTANT CELLS AND COMPARISON WITH THOSE OF PIRARUBICIN

We examined the transport mechanisms of daunorubicin (DNR) and doxorub icin (ADR) in HL60 and HL60/THP cells which were the non-P-glycoprotei n-mediated resistant clone of the parent HL60 cells and showed a low d egree of resistance, and compared them with those of pirarubicin (THP) . In both lines, it appeared that the uptakes of DNR and ADR mere time -, temperature- and concentration-dependent and energy independent, an d the transport of DNR consisted of saturable and nonsaturable compone nts. They were pumped out from the cells time-, temperature- and energ y-dependently. There were no differences in the accumulation amount of either DNR or ADR between HL60 and HL60/THP cells. Comparing the tran sport of DNR or ADR with that of THP, the uptake amounts of DNR and TH P were approximately equal, and were greater than that of ADR in both types of cell. In cis-inhibition experiments, DNR inhibited the THP up take noncompetitively in the parent and resistant cells, in contradict ion of the previously reported result in which ADR showed competitive inhibition (Nagasawa, K, et al., Cancer Chemother. Pharmacol., in pres s). The THP accumulation appeared to be increased by preload of DNR an d ADR, indicating a counter transport. Thus, DNR and ADR as well as TH P might be incorporated via a common carrier-mediated transport system , but DNR uptake in part appeared to follow a nonsaturable transport, and its binding site in the carrier might differ from that of THP and ADR in both HL60 and HL60/THP cells.