title: Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis.
abstract: Chronic inflammation of gastrointestinal tissues is a well-recognized risk factor for the development of epithelial cell-derived malignancies. Although the inflammatory mediators linking chronic inflammation to carcinogenesis are numerous, current information suggests that nitric oxide (NO) contributes to carcinogenesis during chronic inflammation. Inducible nitric oxide synthase (iNOS), expressed by both macrophages and epithelial cells during inflammation, generates the bioreactive molecule NO. In addition to causing DNA lesions, NO can directly interact with proteins by nitrosylation and nitosation reactions. The consequences of protein damage by NO appear to be procarcinogenic. For example, NO inhibits DNA repair enzymes such as human 8-oxodeoxyguanosine DNA glycosylase 1 and blocks apoptosis via nitrosylation of caspases. These cellular events permit DNA damage to accumulate, which is required for the numerous mutations necessary for development of invasive cancer. NO also promotes cancer progression by functioning as an angiogenesis factor. Strategies to inhibit NO generation during chronic inflammation or to scavenge reactive nitrogen species may prove useful in decreasing the risk of cancer development in chronic inflammatory gastrointestinal diseases.
authors.affiliation: Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic, Foundation, and Medical School, Rochester, Minnesota 55905, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jaiswal
authors.forename: N F
authors.initials: NF
authors.lastname: LaRusso
authors.forename: G J
authors.initials: GJ
authors.lastname: Gores
mesh_terms: D000818:Animals; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002908:Chronic Disease; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000209:etiology; D009569:Nitric Oxide / Q000378:metabolism* / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011506:Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D011506:Proteins; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II