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Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis
Sporadic colon cancer is caused predominantly by dietary factors. We have selected bile acids as a focus of this review since high levels of hydrophobic bile acids accompany a Western-style diet, and play a key role in colon carcinogenesis. We describe how bile acid-induced stresses cause cell death...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108627/ https://www.ncbi.nlm.nih.gov/pubmed/21677822 |
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author | Payne, Claire M Bernstein, Carol Dvorak, Katerina Bernstein, Harris |
author_facet | Payne, Claire M Bernstein, Carol Dvorak, Katerina Bernstein, Harris |
author_sort | Payne, Claire M |
collection | PubMed |
description | Sporadic colon cancer is caused predominantly by dietary factors. We have selected bile acids as a focus of this review since high levels of hydrophobic bile acids accompany a Western-style diet, and play a key role in colon carcinogenesis. We describe how bile acid-induced stresses cause cell death in susceptible cells, contribute to genomic instability in surviving cells, impose Darwinian selection on survivors and enhance initiation and progression to colon cancer. The most likely major mechanisms by which hydrophobic bile acids induce stresses on cells (DNA damage, endoplasmic reticulum stress, mitochondrial damage) are described. Persistent exposure of colon epithelial cells to hydrophobic bile acids can result in the activation of pro-survival stress-response pathways, and the modulation of numerous genes/proteins associated with chromosome maintenance and mitosis. The multiple mechanisms by which hydrophobic bile acids contribute to genomic instability are discussed, and include oxidative DNA damage, p53 and other mutations, micronuclei formation and aneuploidy. Since bile acids and oxidative stress decrease DNA repair proteins, an increase in DNA damage and increased genomic instability through this mechanism is also described. This review provides a mechanistic explanation for the important link between a Western-style diet and associated increased levels of colon cancer. |
format | Online Article Text |
id | pubmed-3108627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31086272011-06-14 Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis Payne, Claire M Bernstein, Carol Dvorak, Katerina Bernstein, Harris Clin Exp Gastroenterol Review Sporadic colon cancer is caused predominantly by dietary factors. We have selected bile acids as a focus of this review since high levels of hydrophobic bile acids accompany a Western-style diet, and play a key role in colon carcinogenesis. We describe how bile acid-induced stresses cause cell death in susceptible cells, contribute to genomic instability in surviving cells, impose Darwinian selection on survivors and enhance initiation and progression to colon cancer. The most likely major mechanisms by which hydrophobic bile acids induce stresses on cells (DNA damage, endoplasmic reticulum stress, mitochondrial damage) are described. Persistent exposure of colon epithelial cells to hydrophobic bile acids can result in the activation of pro-survival stress-response pathways, and the modulation of numerous genes/proteins associated with chromosome maintenance and mitosis. The multiple mechanisms by which hydrophobic bile acids contribute to genomic instability are discussed, and include oxidative DNA damage, p53 and other mutations, micronuclei formation and aneuploidy. Since bile acids and oxidative stress decrease DNA repair proteins, an increase in DNA damage and increased genomic instability through this mechanism is also described. This review provides a mechanistic explanation for the important link between a Western-style diet and associated increased levels of colon cancer. Dove Medical Press 2008-12-16 /pmc/articles/PMC3108627/ /pubmed/21677822 Text en © 2008 Payne et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Review Payne, Claire M Bernstein, Carol Dvorak, Katerina Bernstein, Harris Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis |
title | Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis |
title_full | Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis |
title_fullStr | Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis |
title_full_unstemmed | Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis |
title_short | Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis |
title_sort | hydrophobic bile acids, genomic instability, darwinian selection, and colon carcinogenesis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108627/ https://www.ncbi.nlm.nih.gov/pubmed/21677822 |
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