Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Oxford University Press
2012
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| Online Access: | http://hdl.handle.net/1721.1/73993 https://orcid.org/0000-0003-0771-9889 https://orcid.org/0000-0003-4021-1569 https://orcid.org/0000-0002-2196-5691 |
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| author | Fiala, Jeannette Louise Allen Egner, Patricia A. Wiriyachan, Nirachara Ruchirawat, Mathuros Kensler, Kevin H. Wogan, Gerald N. Groopman, John D. Croy, Robert G. Essigmann, John M. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Fiala, Jeannette Louise Allen Egner, Patricia A. Wiriyachan, Nirachara Ruchirawat, Mathuros Kensler, Kevin H. Wogan, Gerald N. Groopman, John D. Croy, Robert G. Essigmann, John M. |
| author_sort | Fiala, Jeannette Louise Allen |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:02:59Z |
| format | Article |
| id | mit-1721.1/73993 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:02:59Z |
| publishDate | 2012 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | mit-1721.1/739932022-09-29T23:18:51Z Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex Fiala, Jeannette Louise Allen Egner, Patricia A. Wiriyachan, Nirachara Ruchirawat, Mathuros Kensler, Kevin H. Wogan, Gerald N. Groopman, John D. Croy, Robert G. Essigmann, John M. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Essigmann, John M. Essigmann, John M. Fiala, Jeannette Louise Allen Wogan, Gerald N. Croy, Robert G. 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. National Institutes of Health (U.S.) (Grant R01 ES016313) National Institutes of Health (U.S.) (Grant P30 ES002109) National Institutes of Health (U.S.) (Grant P01 ES006052) National Institutes of Health (U.S.) (Grant P30 ES003819) 2012-10-15T20:09:29Z 2012-10-15T20:09:29Z 2011-01 2011-01 Article http://purl.org/eprint/type/JournalArticle 1096-6080 1096-6099 http://hdl.handle.net/1721.1/73993 Fiala, J. L. A. et al. “Sulforaphane-Mediated Reduction of Aflatoxin B1-N7-Guanine in Rat Liver DNA: Impacts of Strain and Sex.” Toxicological Sciences 121.1 (2011): 57–62. Web. https://orcid.org/0000-0003-0771-9889 https://orcid.org/0000-0003-4021-1569 https://orcid.org/0000-0002-2196-5691 en_US http://dx.doi.org/ 10.1093/toxsci/kfr026 Toxicological Sciences Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Oxford University Press Prof. Essigmann via Howard Silver |
| spellingShingle | Fiala, Jeannette Louise Allen Egner, Patricia A. Wiriyachan, Nirachara Ruchirawat, Mathuros Kensler, Kevin H. Wogan, Gerald N. Groopman, John D. Croy, Robert G. Essigmann, John M. Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex |
| title | Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex |
| title_full | Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex |
| title_fullStr | Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex |
| title_full_unstemmed | Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex |
| title_short | Sulforaphane-Mediated Reduction of Aflatoxin B-1-N-7-Guanine in Rat Liver DNA: Impacts of Strain and Sex |
| title_sort | sulforaphane mediated reduction of aflatoxin b 1 n 7 guanine in rat liver dna impacts of strain and sex |
| url | http://hdl.handle.net/1721.1/73993 https://orcid.org/0000-0003-0771-9889 https://orcid.org/0000-0003-4021-1569 https://orcid.org/0000-0002-2196-5691 |
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