Abstract
We studied the transport mechanism of pirarubicin (THP) in mononuclear cells (MNCs) obtained from healthy human donors. The THP uptake was time-, temperature-, concentration- and energy (in part)-dependent. The uptake of daunorubicin (DNR) and doxorubicin (ADR) was also concentration-dependent, and the transport of ADR consisted of saturable and nonsaturable components. In cis-inhibition experiments, ADR inhibited both THP and DNR uptake noncompetitively, while DNR showed competitive inhibition of the uptake of THP. The THP uptake rate appeared to be increased by preloading DNR, indicating a trans-stimulatory effect, but not with ADR. These results suggest that THP and DNR were taken up into MNCs via a common carrier-mediated transport system, but that the carrier of ADR might differ from that of THP and DNR. Furthermore, apparent differences in the affinity for the carrier, transport efficacy and substrate specificity of the transporter between MNCs and the human leukemia cell lines (HL60 and K562) were indicated.
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