RELATIONSHIP OF MULTIDRUG-RESISTANCE TO RHODAMINE-123 SELECTIVITY BETWEEN CARCINOMA AND NORMAL EPITHELIAL-CELLS - TAXOL AND VINBLASTINE MODULATE DRUG EFFLUX

Preferential retention and cytotoxicity of Rhodamine-123 (Rho-123) was originally reported in a number of carcinoma cell types isolated from a variety of tissues as compared to normal epithelial cells from a li mited number of other tissues. In the present study, we have examined Rho-123 selectivity in normal and tumor cell lines isolated from the s ame tissue source, i.e., human breast. We found that: (a) in matched p airs of normal and carcinoma breast cells, Rho-123 displays no prefere ntial retention in either cell type; (b) there is no preferential toxi city in carcinoma as compared to normal breast cells; in fact, one of the carcinoma cell lines (MDA-MB231) shows moderate resistance to this dye; (c) all of the human breast cell lines do not express P-glycopro tein-mediated multidrug resistance; (d) the normal monkey kidney epith elial cell line CV-1, which was originally used as a model to demonstr ate the relative resistance of normal epithelial cells to this drug, i s found to express high levels of the mdr-1 gene, is resistant to othe r multidrug-resistant drugs (taxol and vinblastine), and its resistanc e to Rho-123 as well as decreased Rho-123 retention can be reversed by verapamil; and (e) taxol and vinblastine are found to block increased Rho-123 efflux in CV-1 cells. Thus, overall the data suggest that pre ferential retention and cytotoxicity of Rho-123 in carcinoma versus no rmal epithelial cells is related to the differential expression of the mdr-1 gene.