COMPARISON OF DRUG ACCUMULATION IN P-GLYCOPROTEIN-EXPRESSING AND MRP-EXPRESSING HUMAN LEUKEMIA-CELLS

P-glycoprotein- and multidrug resistance-associated protein (MRP)-medi ated multidrug resistance is associated with decreased drug accumulati on. The P-glycoprotein-expressing CCRF-CEM/VLB(100) subline and the MR P-expressing CCRF-CEM/E1000 subline are both 50-fold resistant to daun orubicin. However, accumulation of daunorubicin and rhodamine 123 was 285% reduced in the P-glycoprotein-expressing subline compared to 40-5 0% in the MRP-expressing subline. Further, the CCRF-CEM/E1000 cells we re 30-fold resistant to idarubicin, without reduced accumulation. Vera pamil and SDZ PSC 833 restored daunorubicin and rhodamine 123 accumula tion, while buthionine sulphoximine affected only the CCRF-CEM/E1000 s ubline. We conclude that the verapamil associated change in rhodamine 123 accumulation provides a sensitive functional assay for both P-glyc oprotein- and MRP-mediated MDR. Copyright (C) 1996 Elsevier Science Lt d.