Formation of 8-nitroguanine, a nitrative DNA lesion, in inflammation-related carcinogenesis and its significance.

Chronic infection and inflammation contribute to a substantial part of environmental carcinogenesis. Recently, it has been estimated that chronic inflammation accounts for approximately 25% of cancer cases. Various infectious diseases and physical, chemical, and immunological factors participate in inflammation-related carcinogenesis. Under inflammatory conditions, reactive oxygen and nitrogen species, which are generated from inflammatory and epithelial cells, may play an important role in carcinogenesis by causing DNA damage. 8-Nitroguanine is a mutagenic DNA lesion formed during chronic inflammation. In an earlier publication, our group reported the results of an immunohistochemical analysis of animals infected with the liver fluke Opisthorchis viverrini and demonstrated for the first time that 8-nitroguanine was formed at the sites of carcinogenesis. This DNA lesion was found to accumulate in the carcinogenic process in clinical specimens of cancer-prone inflammatory diseases caused by various pathogens, including human papillomavirus and Epstein-Barr virus. Moreover, strong 8-nitroguanine formation in tumor tissues was closely associated with a poor prognosis. On the basis of these findings, 8-nitroguanine could be a potential biomarker to evaluate the risk of inflammation-related carcinogenesis and the prognosis of cancer patients. In this review, the significance of 8-nitroguanine formation in inflammation-related carcinogenesis and tumor progression will be discussed.