EFFECT OF MULTIDRUG-RESISTANT P-GLYCOPROTEIN GENE-EXPRESSION ON CHLOROALUMINUM TETRASULFONATE PHTHALOCYANINE CONCENTRATION

The effect of multidrug-resistant P-glycoprotein gene expression (MDR1 ) in 3T3 cells on cellular concentrations and cytotoxicity induced by the photodynamic agent chloroaluminum tetrasulfonate phthalocyanine (A ISPc) was evaluated. 3T3 cells transfected with a retroviral vector ex pressing human MDR1 cDNA were resistant to colchicine. Resistant cells incubated with daunomycin accumulated only 40-50% of the quantity of daunomycin accumulated in control cells. Resistant cells incubated wit h daunomycin in the presence of verapamil had intracellular daunomycin concentrations approximately equal to control cells without verapamil . When these MDR1 3T3 cells were incubated with AISPc, cellular concen trations of AISPc did not differ between cells resistant to colchicine and those that were not. Similarly, there was little difference in cy totoxicity demonstrated by Cromium-51 release in the two cell lines ex posed to AISPc and light (675 nm; 6 J/cm2). This study suggests photod ynamic therapy using AISPc may be a useful treatment modality for tumo rs in which the MDR1 P-glycoprotein confers resistance to cancer chemo therapeutics. (C), 1993 Wiley-Liss, Inc.