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Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt

Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly...

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Autores principales: Shaughnessy, Daniel T., Gangarosa, Lisa M., Schliebe, Barbara, Umbach, David M., Xu, Zongli, MacIntosh, Beth, Knize, Mark G., Matthews, Peggy P., Swank, Adam E., Sandler, Robert S., DeMarini, David M., Taylor, Jack A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081825/
https://www.ncbi.nlm.nih.gov/pubmed/21541030
http://dx.doi.org/10.1371/journal.pone.0018707
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author Shaughnessy, Daniel T.
Gangarosa, Lisa M.
Schliebe, Barbara
Umbach, David M.
Xu, Zongli
MacIntosh, Beth
Knize, Mark G.
Matthews, Peggy P.
Swank, Adam E.
Sandler, Robert S.
DeMarini, David M.
Taylor, Jack A.
author_facet Shaughnessy, Daniel T.
Gangarosa, Lisa M.
Schliebe, Barbara
Umbach, David M.
Xu, Zongli
MacIntosh, Beth
Knize, Mark G.
Matthews, Peggy P.
Swank, Adam E.
Sandler, Robert S.
DeMarini, David M.
Taylor, Jack A.
author_sort Shaughnessy, Daniel T.
collection PubMed
description Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00340743.
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spelling pubmed-30818252011-05-03 Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt Shaughnessy, Daniel T. Gangarosa, Lisa M. Schliebe, Barbara Umbach, David M. Xu, Zongli MacIntosh, Beth Knize, Mark G. Matthews, Peggy P. Swank, Adam E. Sandler, Robert S. DeMarini, David M. Taylor, Jack A. PLoS One Research Article Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00340743. Public Library of Science 2011-04-25 /pmc/articles/PMC3081825/ /pubmed/21541030 http://dx.doi.org/10.1371/journal.pone.0018707 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Shaughnessy, Daniel T.
Gangarosa, Lisa M.
Schliebe, Barbara
Umbach, David M.
Xu, Zongli
MacIntosh, Beth
Knize, Mark G.
Matthews, Peggy P.
Swank, Adam E.
Sandler, Robert S.
DeMarini, David M.
Taylor, Jack A.
Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt
title Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt
title_full Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt
title_fullStr Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt
title_full_unstemmed Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt
title_short Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt
title_sort inhibition of fried meat-induced colorectal dna damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081825/
https://www.ncbi.nlm.nih.gov/pubmed/21541030
http://dx.doi.org/10.1371/journal.pone.0018707
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