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.
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Authors | J G Cory, A H Cory, A Lorico, G Rappa, A C Sartorelli |
Journal | Anticancer research
(Anticancer Res)
1997 Sep-Oct
Vol. 17
Issue 5A
Pg. 3185-93
ISSN: 0250-7005 [Print] Greece |
PMID | 9413147
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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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
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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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