REVERSAL OF RESISTANCE TO RHODAMINE-123 IN ADRIAMYCIN-RESISTANT FRIEND-LEUKEMIA CELLS

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (6) , 2626-2631
Abstract
Pleiotropic resistance to rhodamine 123 (Rho-123) in Adriamycin (ADM)-resistant Friend leukemia cells was circumvented by cotreatment with 10 .mu.M verapamil. Increased cytotoxicity corresponded to higher intracellular Rho-123 levels. The verapamil-induced increase of drug accumulation in resistant cells was accounted for at least in part by the blockage or slowing of Rho-123 efflux from these cells. Accumulation and consequent cytotoxicity of Rho-123 in sensitive cells was not increased 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 2 different classes of compounds from resistant cells appears to occur via a similar or common mechanism. The similarities in drug transport between Rho-123 and ADM may have important implications when applied to an in vivo environment.