Oxidative and nitrative DNA damage as biomarker for carcinogenesis with special reference to inflammation

Abstract

Reactive oxygen and nitrogen species are known to participate in a wide variety of human diseases. Oxidative DNAdamage is involved in chemical carcinogenesis and aging. Monocyclic chemicals induce mainly oxidative DNAdamage, whereas polycyclic chemicals can induce oxidative DNA damage in addition to DNA adduct formation. Recently, chronic infection and inflammation have been recognized as important factors for carcinogenesis. Nitrative DNA damage as well as oxidative DNA damage is induced in relation to inflammationrelated carcinogenesis. The authors examined the formation of 8-nitroguanine, a nitrative DNA lesion, in humans and animals under inflammatory conditions. An immunofluorescence labeling study demonstrated that 8-nitroguanine was strongly formed in gastric gland epithelial cells in gastritis patients with H. pylori infection, in hepatocytes in patients with hepatitis C, and in oral epithelium of patients with oral lichen planus. 8-Nitroguanine was also formed in colonic epithelial cells of model mice of inflammatory bowel diseases and patients with ulcerative colitis. Interestingly, 8-nitroguanine was formed at the sites of carcinogenesis regardless of etiology. Therefore, 8-nitroguanine could be used as a potential biomarker to evaluate the risk of inflammation- related carcinogenesis.