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

Ann N Y Acad Sci. 2010 Aug:1203:15-22. doi: 10.1111/j.1749-6632.2010.05602.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Asbestos / adverse effects*
  • Asbestos / toxicity
  • Bacterial Infections / enzymology*
  • Bacterial Infections / microbiology
  • Bacterial Infections / pathology
  • Biomarkers, Tumor / adverse effects
  • Biomarkers, Tumor / physiology
  • Biomarkers, Tumor / toxicity
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • DNA Damage / physiology*
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Guanine / physiology
  • Humans
  • Inflammation Mediators / physiology*
  • Nitric Oxide Synthase Type II / physiology*
  • Parasitic Diseases / enzymology*
  • Parasitic Diseases / parasitology
  • Parasitic Diseases / pathology
  • Virus Diseases / enzymology*
  • Virus Diseases / pathology
  • Virus Diseases / virology

Substances

  • 8-nitroguanine
  • Biomarkers, Tumor
  • Inflammation Mediators
  • Asbestos
  • Guanine
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II