Chemistry meets biology in colitis-associated carcinogenesis
The intestine comprises an exceptional venue for a dynamic and complex interplay of numerous chemical and biological processes. Here, multiple chemical and biological systems, including the intestinal tissue itself, its associated immune system, the gut microbiota, xenobiotics, and metabolites meet...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Informa UK (Informa Healthcare)
2014
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| Online Access: | http://hdl.handle.net/1721.1/91231 https://orcid.org/0000-0002-5811-6853 https://orcid.org/0000-0003-0011-3067 https://orcid.org/0000-0003-0771-9889 https://orcid.org/0000-0001-9307-6116 |
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| author | Mangerich, Aswin Dedon, Peter C. Fox, James G. Tannenbaum, Steven Robert Wogan, Gerald N. |
| author2 | Massachusetts Institute of Technology. Center for Environmental Health Sciences |
| author_facet | Massachusetts Institute of Technology. Center for Environmental Health Sciences Mangerich, Aswin Dedon, Peter C. Fox, James G. Tannenbaum, Steven Robert Wogan, Gerald N. |
| author_sort | Mangerich, Aswin |
| collection | MIT |
| description | The intestine comprises an exceptional venue for a dynamic and complex interplay of numerous chemical and biological processes. Here, multiple chemical and biological systems, including the intestinal tissue itself, its associated immune system, the gut microbiota, xenobiotics, and metabolites meet and interact to form a sophisticated and tightly regulated state of tissue homoeostasis. Disturbance of this homeostasis can cause inflammatory bowel disease (IBD)—a chronic disease of multifactorial etiology that is strongly associated with increased risk for cancer development. This review addresses recent developments in research into chemical and biological mechanisms underlying the etiology of inflammation-induced colon cancer. Beginning with a general overview of reactive chemical species generated during colonic inflammation, the mechanistic interplay between chemical and biological mediators of inflammation, the role of genetic toxicology, and microbial pathogenesis in disease development are discussed. When possible, we systematically compare evidence from studies utilizing human IBD patients with experimental investigations in mice. The comparison reveals that many strong pathological and mechanistic correlates exist between mouse models of colitis-associated cancer, and the clinically relevant situation in humans. We also summarize several emerging issues in the field, such as the carcinogenic potential of novel inflammation-related DNA adducts and genotoxic microbial factors, the systemic dimension of inflammation-induced genotoxicity, and the complex role of genome maintenance mechanisms during these processes. Taken together, current evidence points to the induction of genetic and epigenetic alterations by chemical and biological inflammatory stimuli ultimately leading to cancer formation. |
| first_indexed | 2024-09-23T11:54:22Z |
| format | Article |
| id | mit-1721.1/91231 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:54:22Z |
| publishDate | 2014 |
| publisher | Informa UK (Informa Healthcare) |
| record_format | dspace |
| spelling | mit-1721.1/912312022-09-27T22:43:40Z Chemistry meets biology in colitis-associated carcinogenesis Mangerich, Aswin Dedon, Peter C. Fox, James G. Tannenbaum, Steven Robert Wogan, Gerald N. Massachusetts Institute of Technology. Center for Environmental Health Sciences Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Division of Comparative Medicine Dedon, Peter C. Mangerich, Aswin Dedon, Peter C. Fox, James G. Tannenbaum, Steven Robert Wogan, Gerald N. The intestine comprises an exceptional venue for a dynamic and complex interplay of numerous chemical and biological processes. Here, multiple chemical and biological systems, including the intestinal tissue itself, its associated immune system, the gut microbiota, xenobiotics, and metabolites meet and interact to form a sophisticated and tightly regulated state of tissue homoeostasis. Disturbance of this homeostasis can cause inflammatory bowel disease (IBD)—a chronic disease of multifactorial etiology that is strongly associated with increased risk for cancer development. This review addresses recent developments in research into chemical and biological mechanisms underlying the etiology of inflammation-induced colon cancer. Beginning with a general overview of reactive chemical species generated during colonic inflammation, the mechanistic interplay between chemical and biological mediators of inflammation, the role of genetic toxicology, and microbial pathogenesis in disease development are discussed. When possible, we systematically compare evidence from studies utilizing human IBD patients with experimental investigations in mice. The comparison reveals that many strong pathological and mechanistic correlates exist between mouse models of colitis-associated cancer, and the clinically relevant situation in humans. We also summarize several emerging issues in the field, such as the carcinogenic potential of novel inflammation-related DNA adducts and genotoxic microbial factors, the systemic dimension of inflammation-induced genotoxicity, and the complex role of genome maintenance mechanisms during these processes. Taken together, current evidence points to the induction of genetic and epigenetic alterations by chemical and biological inflammatory stimuli ultimately leading to cancer formation. Massachusetts Institute of Technology. Center for Environmental Health Sciences (ES002109) National Institutes of Health (U.S.) (NIH (CA26731)) 2014-10-29T19:53:34Z 2014-10-29T19:53:34Z 2013-11 Article http://purl.org/eprint/type/JournalArticle 1071-5762 1029-2470 http://hdl.handle.net/1721.1/91231 Mangerich, A., P. C. Dedon, J. G. Fox, S. R. Tannenbaum, and G. N. Wogan. “Chemistry Meets Biology in Colitis-Associated Carcinogenesis.” Free Radic Res 47, no. 11 (November 2013): 958–986. https://orcid.org/0000-0002-5811-6853 https://orcid.org/0000-0003-0011-3067 https://orcid.org/0000-0003-0771-9889 https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.3109/10715762.2013.832239 Free Radical Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Informa UK (Informa Healthcare) Prof. Dedon via Howard Sliver |
| spellingShingle | Mangerich, Aswin Dedon, Peter C. Fox, James G. Tannenbaum, Steven Robert Wogan, Gerald N. Chemistry meets biology in colitis-associated carcinogenesis |
| title | Chemistry meets biology in colitis-associated carcinogenesis |
| title_full | Chemistry meets biology in colitis-associated carcinogenesis |
| title_fullStr | Chemistry meets biology in colitis-associated carcinogenesis |
| title_full_unstemmed | Chemistry meets biology in colitis-associated carcinogenesis |
| title_short | Chemistry meets biology in colitis-associated carcinogenesis |
| title_sort | chemistry meets biology in colitis associated carcinogenesis |
| url | http://hdl.handle.net/1721.1/91231 https://orcid.org/0000-0002-5811-6853 https://orcid.org/0000-0003-0011-3067 https://orcid.org/0000-0003-0771-9889 https://orcid.org/0000-0001-9307-6116 |
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