The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis

Abstract

Chronic inflammation contributes to a substantial part of environmental carcinogenesis. Various infectious diseases and physical, chemical, and immunological factors participate in inflammation-related carcinogenesis. Under inflammatory conditions, reactive oxygen and nitrogen species are generated from inflammatory and epithelial cells, and resulting DNA damage may participate in carcinogenesis. 8-Nitroguanine is a mutagenic DNA lesion formed during chronic inflammation. We performed immunohistochemical analysis, and demonstrated that 8-nitroguanine was formed at the sites of carcinogenesis in animal models and patients with various cancer-prone infectious and inflammatory diseases, caused by parasites, viruses, and asbestos exposure. In asbestos-exposed mice, 8-nitroguanine was formed in bronchial epithelial cells, and it is noteworthy that crocidolite induced significantly more intense 8-nitroguanine formation than chrysotile, inconsistent with their carcinogenic potentials. On the basis of these findings, we have proposed that 8-nitroguanine could be a potential biomarker to evaluate the risk of inflammation-related carcinogenesis.