CHEMOSENSITIZATION AND DRUG ACCUMULATION ASSAYS AS COMPLEMENTARY METHODS FOR THE SCREENING OF MULTIDRUG-RESISTANCE REVERSAL AGENTS

Two methods based on the reversion of adriamycin-resistance or the inc rease of Rhodamine 123 accumulation in a multidrug resistant (MDR) cel l line have been simplified and adapted for the screening of MDR rever sal agents. Both methods are carried out in microtiter plates, are hig hly sensitive and can be easily automated. In both assays verapamil an d the cyclosporine derivative PSC 833 could be detected at concentrati ons lower than 1 and 0.05 mu M, respectively. Depending on the MDR cel l line used, drugs exhibiting the collateral sensitivity phenomenon ca n be selected in the cytotoxicity assay, while interferences due to sa mple toxicity are easily avoided in the dye accumulation assay.