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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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Volume 387, Issue 4 (Apr 2006)


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


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

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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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Somchai Pinlaor, Suksanti Prakobwong, Yusuke Hiraku, Porntip Pinlaor, Umawadee Laothong, and Puangrat Yongvanit
European Journal of Pharmacology, 2010, Volume 638, Number 1-3, Page 134
Renato Moreira Rosa, Nícolas Carlos Hoch, Gabriel Vasata Furtado, Jenifer Saffi, and João Antonio Pêgas Henriques
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2007, Volume 633, Number 1, Page 35
Larissa Ragozo Cardoso de Oliveira, Gláucia Aparecida Gomes Cezário, Carlos Roberto Gonçalves de Lima, Vanessa Cristina Nicolete, Eliana Peresi, Maria Tereza de Síbio, Mariele Cristina Modolo Picka, and Sueli Aparecida Calvi
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2011, Volume 723, Number 2, Page 177
Young-Min Han, Dae-Seop Shin, Yu-Jin Lee, Ismail Ahmed Ismail, Su-Hyung Hong, Dong Cho Han, and Byoung-Mog Kwon
Bioorganic & Medicinal Chemistry Letters, 2011, Volume 21, Number 2, Page 747
Safia Habib, Moinuddin, Asif Ali, and Rashid Ali
Cellular Immunology, 2009, Volume 254, Number 2, Page 117
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Sensors and Actuators B: Chemical, 2009, Volume 137, Number 1, Page 7
Rob J. Mairs and Marie Boyd
Seminars in Nuclear Medicine, 2011, Volume 41, Number 5, Page 334
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Carcinogenesis, 2011, Volume 32, Number 6, Page 888
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Molecular Aspects of Medicine, 2010, Volume 31, Number 2, Page 179
Michael J. Smout, Banchob Sripa, Thewarach Laha, Jason Mulvenna, Robin B. Gasser, Neil D. Young, Jeffrey M. Bethony, Paul J. Brindley, and Alex Loukas
Molecular BioSystems, 2011, Volume 7, Number 5, Page 1367
Avishek Ganguly, Soumya Basu, Kaushik Banerjee, Paramita Chakraborty, Avijit Sarkar, Mitali Chatterjee, and Soumitra Kumar Chaudhuri
Molecular BioSystems, 2011, Volume 7, Number 5, Page 1701
Sandra Regina Miranda, Juliana Noguti, Juliana Gonçalves Carvalho, Celina Tijuko Fujiyama Oshima, and Daniel Araki Ribeiro
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Darren D Browning, In-Kiu Kwon, and Rui Wang
Future Medicinal Chemistry, 2010, Volume 2, Number 1, Page 65
Kasper Broedbaek, Volkert Siersma, Jon T. Andersen, Morten Petersen, Shoaib Afzal, Brian Hjelvang, Allan Weimann, Richard D. Semba, Luigi Ferrucci, and Henrik E. Poulsen
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Danielle G Smith, Tapiwanashe Magwere, and Susan A Burchill
Expert Review of Anticancer Therapy, 2011, Volume 11, Number 2, Page 229
Vonetta M Williams, Maria Filippova, Ubaldo Soto, and Penelope J Duerksen-Hughes
Future Virology, 2011, Volume 6, Number 1, Page 45
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Journal of Pineal Research, 2010, Volume 49, Number 3, Page 271
Yusuke Hiraku, Shosuke Kawanishi, Takamichi Ichinose, and Mariko Murata
Annals of the New York Academy of Sciences, 2010, Volume 1203, Number 1, Page 15
Caleb E. Finch, Todd E. Morgan, Valter D. Longo, and Joao P. De Magalhaes
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Bioscience, Biotechnology, and Biochemistry, 2010, Volume 74, Number 4, Page 766
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Carcinogenesis, 2010, Volume 31, Number 4, Page 687
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Environmental Health and Preventive Medicine, 2010, Volume 15, Number 2, Page 63
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Amino Acids, 2010, Volume 38, Number 1, Page 319
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Cancer Science, 2010, Volume 101, Number 1, Page 281
Masaki Katsurahara, Yoshinao Kobayashi, Motoh Iwasa, Ning Ma, Hiroyuki Inoue, Naoki Fujita, Kyosuke Tanaka, Noriyuki Horiki, Esteban C. Gabazza, and Yoshiyuki Takei
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Stephen P. Jackson and Jiri Bartek
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Molecular Nutrition & Food Research, 2009, Volume 53, Number 10, Page 1316
Toshio Imai, Mai Hasumura, Young-Man Cho, Yoshio Ota, Shigeaki Takami, Masao Hirose, and Akiyoshi Nishikawa
Cancer Science, 2009, Volume 100, Number 10, Page 1794
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Olga Lorenz, Wolfram Parzefall, Eveline Kainzbauer, Helge Wimmer, Bettina Grasl-Kraupp, Christopher Gerner, and Rolf Schulte-Hermann
PROTEOMICS - CLINICAL APPLICATIONS, 2009, Volume 3, Number 8, Page 947
Yong-Chang Wei, Fu-Ling Zhou, Da-Lin He, Ji-Rong Bai, Hui Ding, Xin-Yang Wang, and Ke-Jun Nan
The International Journal of Neuropsychopharmacology, 2009, Volume 12, Number 08, Page 1089
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Digestive Diseases and Sciences, 2009, Volume 54, Number 9, Page 1857
Dunyaporn Trachootham, Jerome Alexandre, and Peng Huang
Nature Reviews Drug Discovery, 2009, Volume 8, Number 7, Page 579
Linda A. Feagins, Rhonda F. Souza, and Stuart J. Spechler
Nature Reviews Gastroenterology & Hepatology, 2009, Volume 6, Number 5, Page 297
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Kazuya MATSUDA, Kanako SAKAGUCHI, Shushi YAMAMOTO, Takafumi HIGASHI, Kazuyuki SUZUKI, Kiyoshi TAGUCHI, Masateru KOIWA, and Hiroyuki TANIYAMA
Journal of Veterinary Medical Science, 2009, Volume 71, Number 2, Page 221
Auemduan Prawan, Benjaporn Buranrat, Upa Kukongviriyapan, Banchob Sripa, and Veerapol Kukongviriyapan
Journal of Cancer Research and Clinical Oncology, 2009, Volume 135, Number 4, Page 515
Izumi Yuasa, Ning Ma, Hisashi Matsubara, Yoshihiro Fukui, and Yukitaka Uji
Japanese Journal of Ophthalmology, 2008, Volume 52, Number 4, Page 314
Masayuki Tatemichi, Tsutomu Ogura, and Hiroyasu Esumi
European Journal of Cancer Prevention, 2009, Volume 18, Number 1, Page 1
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Current Opinion in Gastroenterology, 2008, Volume 24, Number 3, Page 349
Yukari Totsuka, Rena Nishigaki, Takeji Takamura-Enya, Nobuo Kawahara, Takashi Sugimura, and Keiji Wakabayashi
Genes and Environment, 2007, Volume 29, Number 2, Page 54
Ning Ma, Michiko Kawanishi, Yusuke Hiraku, Mariko Murata, Guang-Wu Huang, Yuanjiao Huang, Dian-Zhong Luo, Wei-Guang Mo, Yoshihiro Fukui, and Shosuke Kawanishi
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Brandon G. Bentz, Neal D. Hammer, Brett Milash, Slobodanka Klein, David M. Burnett, James A. Radosevich, and G. Kenneth Haines, III
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William O. Osburn, Baktiar Karim, Patrick M. Dolan, Guosheng Liu, Masayuki Yamamoto, David L. Huso, and Thomas W. Kensler
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Yuichi Kuroiwa, Yuji Ishii, Takashi Umemura, Keita Kanki, Kunitoshi Mitsumori, Akiyoshi Nishikawa, Hiroyuki Nakazawa, and Masao Hirose
Cancer Science, 2007, Volume 98, Number 7, Page 949
Katia Aquilano, Giuseppe Filomeni, Sara Baldelli, Sara Piccirillo, Angelo De Martino, Giuseppe Rotilio, and Maria Rosa Ciriolo
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Xing-Qiao Wen, Xiao-Juan Li, Zu-Lan Su, Yong Liu, Xiang-Fu Zhou, Yu-Bin Cai, Wen-Tao Huang, Xin Gao, and Gail S. Prins
Asian Journal of Andrology, 2007, Volume 9, Number 2, Page 206
Yoko Hoki, Yusuke Hiraku, Ning Ma, Mariko Murata, Akihiko Matsumine, Masato Nagahama, Ken Shintani, Atsumasa Uchida, and Shosuke Kawanishi
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Human Genetics, 2007, Volume 121, Number 2, Page 161
Gavin P. Dunn, Catherine M. Koebel, and Robert D. Schreiber
Nature Reviews Immunology, 2006, Volume 6, Number 11, Page 836

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