Document Detail


Potentiation of mitomycin C cytotoxicity by glutathione depletion in a multi-drug resistant mouse leukemia cell line.
MedLine Citation:
PMID:  1451095     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study was undertaken to elucidate the mechanism of cross-resistance to mitomycin C (MMC) in a multi-drug resistant mouse leukemia cell line (P388/R-84). The P388/R-84 cells were 6.2-fold more resistant to MMC as compared to the sensitive cells (P388/S). Since oxygen radical formation has been suggested to be important in MMC cytotoxicity, MMC-dependent peroxidation of membrane lipids (an index of oxygen radical formation) was compared in these cell lines. MMC-dependent lipid peroxidation was 2.56-fold higher using P388/S cell extract when compared to that of P388/R-84 cells. Depletion of cellular glutathione (GSH) levels in the resistant cells produced a 1.76-fold increase in MMC-dependent lipid peroxidation. MMC cytotoxicity was also increased significantly by GSH depletion in P388/R-84 cells. These results suggest that cellular resistance to MMC in P388/R-84 cells may, at least in part, be due to the reduced formation of oxyradicals in these cells.
Authors:
B H Xu; S V Singh
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer letters     Volume:  66     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  1992 Sep 
Date Detail:
Created Date:  1993-01-04     Completed Date:  1993-01-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  49-53     Citation Subset:  IM    
Affiliation:
Mercy Cancer Center, Mercy Hospital of Pittsburgh, PA 15219.
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MeSH Terms
Descriptor/Qualifier:
Animals
Drug Resistance
Drug Screening Assays, Antitumor
Drug Synergism
Glutathione / deficiency*,  metabolism
Leukemia P388 / drug therapy*,  metabolism
Lipid Peroxidation / drug effects
Mice
Mitomycin / pharmacology*,  toxicity
Reactive Oxygen Species / metabolism
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA 50638/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 50-07-7/Mitomycin; 70-18-8/Glutathione

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


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