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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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IMPACT FACTOR 2016: 3.273

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1437-4315
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Volume 387, Issue 4 (Apr 2006)

Issues

Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis

Shosuke Kawanishi
  • Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yusuke Hiraku
  • Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Somchai Pinlaor
  • Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507, Japan, Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Ning Ma
Published Online: 2006-04-11 | DOI: https://doi.org/10.1515/BC.2006.049

Abstract

Infection and chronic inflammation are proposed to contribute to carcinogenesis through inflammation-related mechanisms. Infection with hepatitis C virus, Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are important risk factors for hepatocellular carcinoma (HCC), gastric cancer and cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with colon carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We performed a double immunofluorescence labeling study and found that nitrative and oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS) was expressed in epithelial cells and inflammatory cells at the site of carcinogenesis in humans and animal models. Antibacterial, antiviral and antiparasitic drugs dramatically diminished the formation of these DNA lesion markers and iNOS expression. These results suggest that oxidative and nitrative DNA damage occurs at the sites of carcinogenesis, regardless of etiology. Therefore, it is considered that excessive amounts of reactive nitrogen species produced via iNOS during chronic inflammation may play a key role in carcinogenesis by causing DNA damage. On the basis of our results, we propose that 8-nitroguanine is a promising biomarker to evaluate the potential risk of inflammation-mediated carcinogenesis.

Keywords: carcinogenesis; DNA damage; inducible nitric oxide synthase; inflammation; 8-nitroguanine; 8-oxo-7,8-dihydro-2′-deoxyguanosine

About the article

Corresponding author


Published Online: 2006-04-11

Published in Print: 2006-04-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.049.

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