8-Nitroguanine, a product of nitrative DNA damage caused by reactive nitrogen species: Formation, occurrence, and implications in inflammation and carcinogenesis

Hiroshi Ohshima, Tomohiro Sawa, Takaaki Akaike

Research output: Contribution to journalReview articlepeer-review

92 Citations (Scopus)

Abstract

The authors review studies on 8-nitroguanine (8-NO2-G) formed by reactions of guanine, guanosine, and 2′-deoxyguanosine, either free or in DNA or RNA with reactive nitrogen species (RNS) generated from peroxynitrite, the myeloperoxidase-H2O2-nitrite system, and others. Use of antibodies against 8-NO2-G lias revealed increased formation of 8-NO2-G in various pathological conditions, including RNA virus-induced pneumonia in mice, intrahepatic bile ducts of hamsters infected with the liver fluke Opisthorchis viverrini, and gastric mucosa of patients with Helicobacter pylori-induced gastritis. Immunoreactivity has been found in the cytosol as well as in the nucleus of inflammatory cells and epithelial cells in inflamed tissues, but not in normal tissues. 8-NO2-G in DNA is potentially mutagenic, yielding G:C to T:A transversion, possibly through its rapid depurination to form an apurinic site and/or miscoding with adenine. 8-NO2-G in RNA may interfere with RNA functions and metabolism. Nitrated guanine nucleosides and nucleotides in the nucleotide pool may contribute to oxidative stress via production of superoxide mediated by various reductases and may disturb or modulate directly various important enzymes such as GTP-binding proteins and cGMP-dependent enzymes. Further studies are warranted to establish the roles of 8-NO2-G in various pathopliysiological conditions and inflammation-associated cancer.

Original languageEnglish
Pages (from-to)1033-1045
Number of pages13
JournalAntioxidants and Redox Signaling
Volume8
Issue number5-6
DOIs
Publication statusPublished - 2006 May 1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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