LOCALIZATION OF ANTHRACYCLINE ACCUMULATION IN SENSITIVE AND RESISTANTUROTHELIAL TUMOR-CELL LINES

Emergence of resistance to chemotherapy is a serious clinical problem. Our aim was to investigate anthracycline uptake in sensitive and resi stant urothelial cancer cell lines and to manipulate uptake by resista nt cells. Anthracyclines exhibit natural fluorescence; therefore, the techniques used for detection were high-resolution fluorescence image analysis and confocal microscopy. Different patterns of intracellular drug distribution were observed in the two cell lines. Sensitive cells showed predominantly nuclear drug localization, while in resistant ce lls there was nuclear and cytoplasmic fluorescence. Manipulation of dr ug uptake by resistant cells was achieved using an essential fatty aci d, gammalinolenic acid, and the calcium channel blocker, verapamil. Bo th substances increased drug uptake in resistant cells, with verapamil producing patterns of intracellular drug distribution in resistant ce lls similar to those of sensitive cells.