ESTABLISHMENT AND CHARACTERIZATION OF DOX ORUBICIN-RESISTANT HUMAN BLADDER-CANCER CELL-LINE, RT112 D21/

By exposing the established human bladder cancer cell-line RT112 to pr ogressively higher concentrations of doxorubicin over a period of 10 m onths, a doxorubicin-resistant human bladder cancer cell-line, RT112/D 21 was selected. RT112/D21 was 143 times more resistant to doxorubici than the RT112 parent cell-line and exhibited cross-resistance to doxo rubicin analogon epirubicin and to vinca-alcaloid vinblastine, but not to cisplatin and methotrexate. Unlike the RT112 parent, the resistant subline showed a higher produciton of p-glycoprotein (p-gp) in the im munostaining with monoclonal antibody C219 against mdr1-gen product p- gp. Functional efflux studies with fluorescent p-gp-substrate rhodamin e 123 indicated that the resistance exhibited by the RT112/D21 line wa s mainly due to a reduced intracellular concentration of antineoplasti c p-gp-substrates. These two lines with defined chemosensitivity are c onsidered to be a good standard and a useful model for developing new chemotherapeutic strategies against multidrug-resistant bladder cancer .