501. Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis.
- Author
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Pinlaor S, Hiraku Y, Ma N, Yongvanit P, Semba R, Oikawa S, Murata M, Sripa B, Sithithaworn P, and Kawanishi S
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine, Animals, Cholangiocarcinoma parasitology, Cholangiocarcinoma pathology, Cricetinae, Deoxyguanosine biosynthesis, Disease Models, Animal, Gene Expression Regulation, Guanine biosynthesis, Heme Oxygenase (Decyclizing) genetics, Heme Oxygenase-1, Inflammation complications, Liver metabolism, Liver parasitology, Liver pathology, Nitric Oxide, Nitric Oxide Synthase genetics, Nitric Oxide Synthase Type II, Opisthorchiasis genetics, Opisthorchiasis pathology, Oxidation-Reduction, Cholangiocarcinoma etiology, DNA Damage physiology, Deoxyguanosine analogs & derivatives, Guanine analogs & derivatives, Opisthorchiasis complications, Opisthorchis
- Abstract
Inflammation mediated by infection is an important factor causing carcinogenesis. Opisthorchis viverrini (OV) infection is a risk factor of cholangiocarcinoma (CHCA), probably through chronic inflammation. Formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) were assessed in the liver of hamsters infected with OV. We newly produced specific anti-8-nitroguanine antibody without cross-reaction. Double immunofluorescence staining revealed that 8-oxodG and 8-nitroguanine were formed mainly in the same inflammatory cells and epithelium of bile ducts from day 7 and showed the strongest immunoreactivity on days 21 and 30, respectively. It is noteworthy that 8-oxodG and 8-nitroguanine still remained in epithelium of bile ducts on day 180, although amount of alanine aminotransferase activity returned to normal level. A time course of 8-nitroguanine was associated with iNOS expression. Furthermore, this study demonstrated that HO-1 expression and subsequent iron accumulation may be involved in enhancement of oxidative DNA damage in epithelium of small bile ducts. In conclusion, nitrative and oxidative DNA damage via iNOS expression in hamsters infected with OV may participate in CHCA carcinogenesis.
- Published
- 2004
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