Exploring Multidrug Resistance Using Rhodamine 123

Accumulation of the dye rhodamine 123 was characterized by fluorescence in murine leukemia P388 cells and the Adriamycin-resistant subline, P388/ADR. Dye uptake by P388 cells was a slow, temperature-sensitive process, and involved binding at relatively hydrophobic and heterogeneous loci. Dye uptake by P388/ADR cells was temperature-insensitive, a steady state was quickly achieved, and the fluorescence emission spectrum suggested a relatively hydrophilic dye-binding site. Treatment of P388/ADR cells with verapamil resulted in enhanced accumulation of dye at hydrophobic loci. The fluorescence studies suggest that this dye may not reach the cytoplasm of P388/ADR cells, a result which may have implications with regard to the mechanism of multidrug resistance.