Genetic and epigenetic damage induced by reactive nitrogen species: implications in carcinogenesis

Chronic infection and inflammation are recognized risk factors for human cancer at various sites. Infection and inflammation can activate and induce a variety of oxidant-generating enzymes, including NADPH oxidase and inducible nitric oxide synthase. Reactive oxygen and nitrogen species produced by such enzymes react with each other to generate new and more potent reactive species. These oxidants not only can damage DNA and induce mutations, but also can activate oncogene products and/or inactivate tumor-suppressor proteins, thus contributing to most processes of carcinogenesis. Appropriate treatment of inflammation should be further explored for chemoprevention of human cancers, especially those associated with chronic inflammation. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.