title: Repeated infection with Opisthorchis viverrini induces accumulation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanine in the bile duct of hamsters via inducible nitric oxide synthase.
abstract: Chronic inflammation induced by repeated infection with Opisthorchis viverrini has been postulated to be a risk factor for cholangiocarcinoma. To clarify the mechanism of carcinogenesis induced by repeated O.viverrini infection, we investigated the timecourse of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, inducible nitric oxide synthase (iNOS) expression, nitric oxide production and pathological features in hamsters with two (2-IF) or three (3-IF) O.viverrini infections. Inflammatory cell infiltration triggered by repeated infection (3-IF > 2-IF > 1-IF) was earlier than by single infection (1-IF). HPLC coupled with an electrochemical detector revealed that 8-oxodG level in the liver was the highest on day 3 in 3-IF and day 7 in 2-IF, earlier than that on day 21 in 1-IF. Notably, a double immunofluorescence study revealed that formation of 8-nitroguanine and 8-oxodG appeared to increase in the epithelium of bile ducts in the order 3-IF > 2-IF > 1-IF after the decrease in inflammatory cells. This may be explained by the fact that repeated infection increased iNOS expression in the epithelium of bile ducts in the order 3-IF > 2-IF > 1-IF on day 90. Proliferating cell nuclear antigen accumulated in the epithelium of bile ducts on day 90 after repeated O.viverrini infection, supporting the hypothesis that cell proliferation was promoted by inflammation-mediated DNA damage. In conclusion, more frequent O.viverrini infection can induce the expression of iNOS not only in inflammatory cells but also in the epithelium of bile ducts and subsequently cause nitrosative and oxidative damage to nucleic acids, which may participate in the initiation and/or promotion steps of cholangiocarcinoma development.
authors.affiliation: Department of Environmental and Molecular Medicine and Department of Anatomy, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: Reiji
authors.initials: R
authors.lastname: Semba
authors.forename: Shinji
authors.initials: S
authors.lastname: Oikawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.forename: Paiboon
authors.initials: P
authors.lastname: Sithithaworn
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism; D009889:Opisthorchiasis / Q000378:metabolism*; D009891:Opisthorchis / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen; D013997:Time Factors
chemical_list: C095838:8-nitroguanine; D009566:Nitrates; D009573:Nitrites; D018809:Proliferating Cell Nuclear Antigen; D008315:Malondialdehyde; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D000410:Alanine Transaminase