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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.
AuthorsJ G Cory, A H Cory, A Lorico, G Rappa, A C Sartorelli
JournalAnticancer research (Anticancer Res) 1997 Sep-Oct Vol. 17 Issue 5A Pg. 3185-93 ISSN: 0250-7005 [Print] Greece
PMID9413147 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Arsenites
  • Enzyme Inhibitors
  • Isoquinolines
  • Propionates
  • Quinolines
  • Rhodamines
  • Rhodamine 123
  • 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone
  • verlukast
  • Cyclosporine
  • Reserpine
  • Adenosine Triphosphate
  • Verapamil
  • Genistein
  • Ribonucleotide Reductases
  • arsenite
  • Daunorubicin
Topics
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Arsenites (pharmacology)
  • Biological Transport (drug effects)
  • Cyclosporine (pharmacology)
  • Daunorubicin (metabolism)
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors (pharmacology)
  • Genistein (pharmacology)
  • Isoquinolines (pharmacology)
  • Leukemia L1210
  • Mice
  • Propionates (pharmacology)
  • Quinolines (pharmacology)
  • Reserpine (pharmacology)
  • Rhodamine 123
  • Rhodamines (metabolism)
  • Ribonucleotide Reductases (antagonists & inhibitors, metabolism)
  • Temperature
  • Verapamil (pharmacology)

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