title: Altered efflux properties of mouse leukemia L1210 cells resistant to 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone.
abstract: A mouse leukemia L1210 cell line, denoted MQ-580, that was selected for resistance to the ribonucleotide reductase inhibitor, 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ), in addition to having altered properties at the ribonucleotide reductase site had other alterations that contributed to its resistant phenotype; these included the expression of p-glycoprotein and the multi-drug resistance associated protein (MRP). The efflux of rhodamine 123 (Rh-123) or daunomycin (Dau) was greatly increased in MQ-580 cells compared to parental wild-type (WT) cells. The effluxes of Rh-123 and Dau were ATP- and temperature-dependent. The p-glycoprotein inhibitors, verapamil, cyclosporin A and reserpine blocked the efflux of both Rh-123 and Dau. In contrast, the inhibitors of MRP, MK571, BSO-treatment, arsenite and genistein did not block the efflux of either Rh-123 or Dau from MQ-580 cells. These findings suggest that the p-glycoprotein is the major transporter involved in effluxing Rh-123 and Dau from MQ-580 cells.
authors.affiliation: Department of Biochemistry, East Carolina University School of Medicine, Greenville, NC 27858, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Cory
authors.forename: A H
authors.initials: AH
authors.lastname: Cory
authors.forename: A
authors.initials: A
authors.lastname: Lorico
authors.forename: G
authors.initials: G
authors.lastname: Rappa
authors.forename: A C
authors.initials: AC
authors.lastname: Sartorelli
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D007939:Leukemia L1210; D051379:Mice; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013696:Temperature; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018053:Arsenites; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D011422:Propionates; D011804:Quinolines; D012235:Rhodamines; D020112:Rhodamine 123; C013118:4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone; C059141:verlukast; D016572:Cyclosporine; D012110:Reserpine; D000255:Adenosine Triphosphate; D014700:Verapamil; D019833:Genistein; D012264:Ribonucleotide Reductases; C015001:arsenite; D003630:Daunorubicin