[Use of rhodamine 123 for the detection of multidrug resistance].

Multidrug resistance (MDR) is characterized by the overexpression of P-glycoprotein (Pgp), which is responsible for decreasing drug uptake and/or increasing drug efflux in resistant cells. Although Pgp has a broad-spectrum specificity, this protein seems to react preferentially with amphiphilic and cationic molecules. Rhodamine 123 (R123) is widely used as a marker for mitochondria in living cells and its uptake is dependent on plasma and mitochondrial membrane potential. More recently, cross-resistance to R123 in cells resistant to adriamycin has been demonstrated and a correlation between expression of Pgp and reduced intracellular accumulation of R123 has been shown. The measurement of R123 uptake or efflux allows the characterization of cells displaying a MDR phenotype with overexpression of Pgp, even with low levels of resistance. Other proteins have now been identified which play a role in resistance and in drug transport, including MRP. For this reason we need to determine if R123 is transported only by Pgp or if R123 is a substrate for transport by other drug resistance proteins as well. We also discuss the possibilities of using several techniques based on fluorescence with R123 in order to fully characterize cells by measuring both Pgp activity and its presence/localization.