The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis.
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.
Hiraku
Yusuke
Y
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan. y-hiraku@doc.medic.mie-u.ac.jp
Kawanishi
Shosuke
S
Ichinose
Takamichi
T
Murata
Mariko
M
D000818:Animals; D001194:Asbestos / Q000009:adverse effects* / Q000633:toxicity; D001424:Bacterial Infections / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000009:adverse effects / Q000502:physiology / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage / Q000502:physiology*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D010272:Parasitic Diseases / Q000201:enzymology* / Q000469:parasitology / Q000473:pathology; D014777:Virus Diseases / Q000201:enzymology* / Q000473:pathology / Q000821:virology
C095838:8-nitroguanine; D014408:Biomarkers, Tumor; D018836:Inflammation Mediators; D001194:Asbestos; D006147:Guanine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II