| The influence of glutathione and detoxifying enzymes on DNA damage induced by 2-alkenals in primary rat hepatocytes and human lymphoblastoid cells. | |
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MedLine Citation:
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PMID: 7703365 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The reaction of 2-alkenals with GSH to form GSH conjugates by Michael addition is a major detoxification pathway. The reaction proceeds at a much higher rate under catalysis by glutathione S-transferase (GST) than the non-enzymatic reaction. Oxidation of 2-alkenals to the corresponding acids by cytosolic and microsomal fraction of rat liver also contributes to detoxification. Primary rat hepatocytes rich in GSH and proficient for GST and other metabolizing enzymes consume much more alkenal than human lymphoblastoid cells (Namalva cells), that are poor in GSH and in metabolic activities. In Namalva cells DNA single strand breaks were induced by much lower concentrations of acrolein, crotonaldehyde and (E)-2-hexenal than in primary rat hepatocytes. In both cell systems intracellular GSH depletion by 2-alkenals proceeds in a dose dependent manner, approaching about 20% of pretreatment level before DNA damage becomes detectable. GSH conjugates of (E)-2-hexenal and (2E,6Z)-2,6-nonadienal induce DNA damage in Namalva cells at high concentrations (1.5 mM). In the absence of GSH these conjugates decompose slowly into aldehyde and GSH. Although the rate of decomposition is only about 10(-4) times that of Michael adduct formation, such GSH conjugates could potentially function as transport molecules for 2-alkenals, if they reach tissues low in GSH and GST. |
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Authors:
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G Eisenbrand; J Schuhmacher; P Gölzer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemical research in toxicology Volume: 8 ISSN: 0893-228X ISO Abbreviation: Chem. Res. Toxicol. Publication Date: 1995 Jan-Feb |
Date Detail:
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Created Date: 1995-05-10 Completed Date: 1995-05-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 40-6 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acrolein
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metabolism,
toxicity* Aldehydes / metabolism, toxicity* Animals Cell Line DNA Damage* DNA, Single-Stranded / drug effects Glutathione / metabolism* Glutathione Transferase / physiology* Hexobarbital / metabolism, toxicity* Humans Liver / metabolism Lymphocytes / metabolism Male Rats |
| Chemical | |
Reg. No./Substance:
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0/Aldehydes; 0/DNA, Single-Stranded; 107-02-8/Acrolein; 4170-30-3/2-butenal; 56-29-1/Hexobarbital; 70-18-8/Glutathione; EC 2.5.1.18/Glutathione Transferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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