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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.
AuthorsYusuke Hiraku, Shosuke Kawanishi, Takamichi Ichinose, Mariko Murata
JournalAnnals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1203 Pg. 15-22 (Aug 2010) ISSN: 1749-6632 [Electronic] United States
PMID20716278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • 8-nitroguanine
  • Biomarkers, Tumor
  • Inflammation Mediators
  • Asbestos
  • Guanine
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
Topics
  • Animals
  • Asbestos (adverse effects, toxicity)
  • Bacterial Infections (enzymology, microbiology, pathology)
  • Biomarkers, Tumor (adverse effects, physiology, toxicity)
  • Cell Transformation, Neoplastic (chemically induced, genetics, pathology)
  • DNA Damage (physiology)
  • Guanine (adverse effects, analogs & derivatives, physiology)
  • Humans
  • Inflammation Mediators (physiology)
  • Nitric Oxide Synthase Type II (physiology)
  • Parasitic Diseases (enzymology, parasitology, pathology)
  • Virus Diseases (enzymology, pathology, virology)

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