Chemical basis of inflammation-induced carcinogenesis.
Chronic inflammation induced by biological, chemical, and physical factors has been associated with increased risk of human cancer at various sites. Inflammation activates a variety of inflammatory cells, which induce and activate several oxidant-generating enzymes such as NADPH oxidase, inducible nitric oxide synthase, myeloperoxidase, and eosinophil peroxidase. These enzymes produce high concentrations of diverse free radicals and oxidants including superoxide anion, nitric oxide, nitroxyl, nitrogen dioxide, hydrogen peroxide, hypochlorous acid, and hypobromous acid, which react with each other to generate other more potent reactive oxygen and nitrogen species such as peroxynitrite. These species can damage DNA, RNA, lipids, and proteins by nitration, oxidation, chlorination, and bromination reactions, leading to increased mutations and altered functions of enzymes and proteins (e.g., activation of oncogene products and/or inhibition of tumor-suppressor proteins) and thus contributing to the multistage carcinogenesis process. Appropriate treatment of inflammation should be explored further for chemoprevention of human cancers.
Ohshima
Hiroshi
H
Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France. ohshima@iarc.fr
Tatemichi
Masayuki
M
Sawa
Tomohiro
T
D004249:DNA Damage; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced* / Q000517:prevention & control; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D009153:Mutagens; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species