Journal Article

Repeated infection with <i>Opisthorchis viverrini</i> induces accumulation of 8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxyguanine in the bile duct of hamsters via inducible nitric oxide synthase

Somchai Pinlaor, Ning Ma, Yusuke Hiraku, Puangrat Yongvanit, Reiji Semba, Shinji Oikawa, Mariko Murata, Banchob Sripa, Paiboon Sithithaworn and Shosuke Kawanishi

in Carcinogenesis

Volume 25, issue 8, pages 1535-1542
Published in print August 2004 | ISSN: 0143-3334
Published online August 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh157
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

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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.

Keywords: ALT, alanine aminotransferase; CHCA, cholangiocarcinoma; GSH, reduced glutathione; HPLC-ECD, electrochemical detector coupled to HPLC; 1-IF, single infection; 2-IF, two infections; 3-IF, three infections; iNOS, inducible nitric oxide synthase; LPO, lipid peroxidation; MDA, malondialdehyde; ONOO−, peroxynitrite; 8-oxodG, 8-oxo-7,8-dihydro-2′-deoxyguanosine; PBS, phosphate-buffered saline; PCNA, proliferating cell nuclear antigen; RSA, rabbit serum albumin; TBARS, thiobarbituric acid-reactive substances

Journal Article.  5661 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.