| Induction of glutathione transferases and NAD(P)H:quinone reductase by fumaric acid derivatives in rodent cells and tissues. | |
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MedLine Citation:
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PMID: 2123743 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dimethyl fumarate and dimethyl maleate are potent inducers of cytosolic NAD(P)H:(quinone acceptor) oxidoreductase (here designated quinone reductase) activity in Hepa 1c1c7 murine hepatoma cells in culture, whereas fumaric and maleic acids are much less potent, in agreement with the much greater reactivity of the esters as Michael reaction acceptors (P. Talalay, M. J. De Long, and H. J. Prochaska, Proc. Natl. Acad. Sci. USA, 85:8261-8265, 1988). Dimethyl fumarate also induced quinone reductase in mutants of the Hepa 1c1c7 cell line that were either defective in the Ah receptor or in cytochrome P1-450 activity, thereby establishing that this compound is a monofunctional inducer (H. J. Prochaska and P. Talalay, Cancer Res., 48: 4776-4782, 1988). Addition of dimethyl fumarate to the diet of female CD-1 mice and female Sprague-Dawley rats at 0.2-0.5% concentrations elevated cytosolic glutathione transferases and quinone reductase activities in a variety of organs, whereas much higher concentrations of fumaric acid were only marginally active. The widespread induction of such detoxication enzymes by dimethyl fumarate suggests the potential value of this compound as a protective agent against chemical carcinogenesis and other forms of electrophile toxicity. This proposal is supported by the finding that the concentrations of dimethyl fumarate required to obtain substantial enzyme inductions were well tolerated by rodents. Furthermore, the parent fumaric acid has low chronic toxicity and is a naturally occurring metabolic intermediate that is already in the food chain as an additive, and fumarate salts and esters are used for therapeutic purposes in man. |
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Authors:
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S R Spencer; C A Wilczak; P Talalay |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 50 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1990 Dec |
Date Detail:
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Created Date: 1991-01-23 Completed Date: 1991-01-23 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 7871-5 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cytosol / enzymology Enzyme Induction Female Fumarates / pharmacology* Ligands* Liver / drug effects, enzymology Liver Neoplasms, Experimental / enzymology* Mice Mutation NAD(P)H Dehydrogenase (Quinone) Organ Specificity Quinone Reductases / biosynthesis* Rats Rats, Inbred Strains Species Specificity Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA44530/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fumarates; 0/Ligands; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.99.-/Quinone Reductases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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