Document Detail

Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia.
MedLine Citation:
PMID:  445418     Owner:  NLM     Status:  MEDLINE    
Significantly decreased uptake and retention of daunorubicin (DAU) and Adriamycin (ADR) have been reported in sublines of P388 leukemia resistant to these anthracyclines. We studied the effects of inhibitors of oxidative phosphorylation on uptake and retention of DAU and ADR in order to characterize the transport process for these anthracyclines and to clarify further the alteration in resistant cells. In glucose-free medium, uptake of DAU and ADR was accelerated by metabolic inhibitors to a greater extent in resistant cells than in sensitive cells. Under these conditions, drug uptake was similar in sensitive and resistant cells. When glucose was added to the incubation medium in the presence of 2,4-dinitrophenol, efflux of DAU from both sensitive and resistant cells was observed. Net efflux of ADR was also observed with the resistant cells, whereas glucose markedly inhibited 2,4-dinitrophenol-stimulated uptake of ADR by the sensitive cells. Furthermore, in sensitive and resistant cells preloaded with ADR and DAU, efflux of the drugs was inhibited by the addition of 2,4-dinitrophenol. These results suggest that there is an active outward transport mechanism for anthracyclines in P388 leukemia cells and that enhanced activity of this efflux process renders cells highly resistant to the cytostatic and cytotoxic effects of ADR and DAU.
M Inaba; H Kobayashi; Y Sakurai; R K Johnson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  39     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1979 Jun 
Date Detail:
Created Date:  1979-08-29     Completed Date:  1979-08-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2200-3     Citation Subset:  IM    
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MeSH Terms
Antimetabolites / pharmacology
Biological Transport, Active / drug effects
Cell Line
Daunorubicin / metabolism*,  pharmacology
Dinitrophenols / pharmacology
Doxorubicin / metabolism*,  pharmacology
Drug Resistance
Leukemia, Experimental / drug therapy,  metabolism*
Reg. No./Substance:
0/Antimetabolites; 0/Dinitrophenols; 20830-81-3/Daunorubicin; 23214-92-8/Doxorubicin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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