| Sulforaphane-mediated reduction of aflatoxin B₁-N⁷-guanine in rat liver DNA: impacts of strain and sex. | |
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MedLine Citation:
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PMID: 21278056 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aflatoxin B₁ (AFB₁) is a DNA-binding toxin that contributes to the burden of liver cancer in tropical areas. AFB₁-DNA adducts are powerful biomarkers that discern individual and population risk from exposure to this carcinogen. The discovery of concordance between the metabolic pathways of the male Fischer rat and humans allowed data from rats to guide the development of chemoprevention strategies employed in clinical trials in high-risk regions. In this study, the variables of strain and sex are studied in the rat model, as a step toward understanding how ethnic differences and sex influence DNA adduct formation and the induction of enzymes by chemoprotective agents. Sulforaphane (SF), which induces phase II enzymes including glutathione S-transferases (GSTs), was evaluated for its ability to induce GST activity and reduce the AFB₁-DNA adducts in livers of both sexes of two rat strains that differ in susceptibility to AFB₁ hepatocarcinogenesis. A dose-dependent relationship was found for SF for both induction of GST and reduction in of AFB₁-N⁷-guanine in both Fischer (sensitive to AFB₁) and Sprague-Dawley rats (relatively resistant). Sprague-Dawley rats exhibited the greatest increase in GST levels and the largest reduction in AFB₁-N⁷-guanine in liver DNA. Males and females of each strain were also compared to determine if the ability of SF to induce GST and reduce AFB₁-N⁷-guanine correlated with gender differences in sensitivity to AFB₁ carcinogenesis. No gender-specific responses to SF were observed. These results support the view that SF induction of liver GST activity may play a role in its chemoprotective activity. |
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Authors:
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Jeannette L A Fiala; Patricia A Egner; Nirachara Wiriyachan; Mathuros Ruchirawat; Kevin H Kensler; Gerald N Wogan; John D Groopman; Robert G Croy; John M Essigmann |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-01-28 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 121 ISSN: 1096-0929 ISO Abbreviation: Toxicol. Sci. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-04-21 Completed Date: 2011-08-16 Revised Date: 2012-05-01 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 57-62 Citation Subset: IM |
Affiliation:
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Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aflatoxin B1
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analogs & derivatives*,
metabolism Animals Anticarcinogenic Agents / pharmacology* DNA / drug effects* Dose-Response Relationship, Drug Female Guanine / analogs & derivatives*, metabolism Liver / drug effects*, metabolism Male Rats Rats, Inbred F344 Rats, Sprague-Dawley Species Specificity Thiocyanates / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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P01 ES006052/ES/NIEHS NIH HHS; P30 ES002109/ES/NIEHS NIH HHS; P30 ES003819/ES/NIEHS NIH HHS; R01 ES016313/ES/NIEHS NIH HHS; R01 ES016313-05/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anticarcinogenic Agents; 0/Thiocyanates; 0/aflatoxin-B1-N7-guanine; 1162-65-8/Aflatoxin B1; 4478-93-7/sulforafan; 73-40-5/Guanine; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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