Journal Article

Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models

Darren N. Seril, Jie Liao, Guang-Yu Yang and Chung S. Yang

in Carcinogenesis

Volume 24, issue 3, pages 353-362
Published in print March 2003 | ISSN: 0143-3334
Published online March 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/24.3.353
Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models

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The chronic inflammatory bowel disease ulcerative colitis (UC) occurs commonly in the US and other Western countries, but its etiology is unknown. An association between UC and an elevated risk for colorectal cancer is well established. UC-associated colorectal carcinogenesis is probably driven by chronic inflammation, but the mechanism is unclear. The morphological development of UC-associated cancer differs from that of its sporadic counterpart. Similarly, detailed molecular analyses have indicated that whereas many of the genetic alterations observed in sporadic colon cancers also occur in UC-associated neoplasms, the timing and frequency of those changes in the setting of UC are different. These histological and molecular signatures may very well be reflective of an inflammation-driven carcinogenesis process in UC patients. Studies in animal models of UC have helped to shed light on the mechanisms of inflammation-driven colorectal carcinogenesis. The available evidence suggests that DNA damage caused by oxidative stress in the characteristic damage–regeneration cycle is a major contributor to colorectal cancer development in UC patients. Based on this concept, iron over-nutrition is proposed as a risk factor and dietary antioxidants as protective factors for UC and associated carcinogenesis.

Keywords: CGH, comparative genomic hybridization; DALM, dysplasia-associated lesion or mass; DSS, dextran sulfate sodium; IBD, inflammatory bowel disease; iNOS, inducible nitric oxide synthase; MHC, major histocompatibility complex; MIN, microsatellite instability; NAC, N-acetylcysteine; NO, nitric oxide; NOS, nitric oxide synthase; RONS, reactive oxygen and nitrogen species; UC, ulcerative colitis

Journal Article.  9995 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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