ESTABLISHMENT AND CHARACTERIZATION OF A MULTIDRUG-RESISTANT HUMAN BLADDER-CARCINOMA CELL-LINE RT112 D21/

A doxorubicin-resistant human bladder carcinoma cell line RT112/D21 wa s established by continuous exposure of the parental line RT112 to inc reasing concentrations of doxorubicin over a period of 9 months. RT112 /D21 cells expressed significantly more P-170 glycoprotein than the pa rental line, and rhodamine 123 efflux, as a functional parameter of P- 170 glycoprotein activity, was increased. RT112/D21 cells were 96 time s more resistant to doxorubicin than RT112 cells, and cross-resistance to epirubicin and vinblastine was present. Sensitivity to methotrexat e and mitomycin C remained unchanged. R-verapamil reversed resistance to doxorubicin, epirubicin and vinblastine in RT112/D21 cells but did not affect sensitivity to methotrexate and mitomycin C. In RT112 cells , R-verapamil had no effect on drug sensitivity. Thus, it may be assum ed that primary or induced MDR1 gene-encoded P-170 glycoprotein expres sion is a relevant mechanism of chemoresistance in transitional cell c arcinoma, and that chemotherapeutic strategies in combination with che mosensitizers improve response rates.