Reversal of Resistance to Rhodamine 123 in Adriamycin-resistant Friend Leukemia Cells1

Pleiotropic resistance to rhodamine 123 (Rho-123) in Adriamycin (ADM)-resistant Friend leukemia cells was circumvented by cotreatment with 10 //M verapamil. Increased cytotoxicity corresponded to higher intracellular Rho-123 levels. The verapamil-induced increase of drug accumulation in resistant cells is accounted for at least in part by the blockage or slowing of Rho123 efflux from these cells. In contrast, accumulation and con sequent cytotoxicity of Rho-123 in sensitive cells are not in creased by verapamil. Similar results were obtained when ADM was used in this cell system. These results suggest that the efflux system for Rho-123 and ADM in sensitive cells is either reduced or absent. Although Rho-123 accumulates specifically in mitochondria and ADM mainly in the nucleus, the loss of these two different classes of compounds from resistant cells appears to occur via a similar or common mechanism. The similarities in drug trans port between Rho-123 and ADM may have important implica tions when applied to an in vivo environment.