2 MULTIDRUG-RESISTANT FRIEND LEUKEMIC-CELL LINES SELECTED WITH DIFFERENT DRUGS EXHIBIT OVERPRODUCTION OF DIFFERENT P-GLYCOPROTEINS

Two Friend leukemic multidrug-resistance (MDR) cell lines were establi shed by exposure to stepwise increased concentrations of rhodamine-123 (RHO) (cell line RR-30) or Adriamycin (ADR) (cell line ARN-15). RR-30 displays preferential resistance to RHO, whereas ARN-15 is more resis tant to ADR. The levels of resistance to other MDR drugs and reversibi lity by verapamil between these two MDR cell lines were somewhat diffe rent. Southern blot, RNase protection, and Western blot analysis using gene-specific probes demonstrated that RR-30 and ARN-15 cells prefere ntially amplified the mdr1 and mdr3 genes, respectively, leading to ov erexpression of the corresponding P-glycoproteins (p-gp). Our results suggest that members of the mdr gene family can be amplified independe ntly by using different selecting agents, which could be responsible f or the differences in the sensitivities to these selecting agents as w ell as to these MDR drugs.