Mutagenicity of 8-nitroguanosine, a product of nitrative nucleoside modification by reactive nitrogen oxides, in mammalian cells

Kazuyoshi Kaneko, Teruo Akuta, Tomohiro Sawa, Ha Won Kim, Shigemoto Fujii, Tatsuya Okamoto, Hitoshi Nakayama, Hajime Ohigashi, Akira Murakami, Takaaki Akaike

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

8-Nitroguanosine is a nitratively modified nucleoside that is formed endogeneously under inflammatory conditions dependent on nitric oxide production, particularly associated with cancer risks. Here, we investigated the mutagenic potential of 8-nitroguanosine in mammalian cells. Treatment with 8-nitroguanosine (10-1000 μM) for 1 h significantly increased (by 6-8 times) the mutation frequency of the xanthine-guanine phosphoribosyltransferase (gpt) gene in AS52 cells without cytotoxic effects. 8-Nitroguanosine treatment induced a G-to-T transversion in gpt gene at position 86. It also significantly increased levels of abasic sites in DNA. These observations suggest that formation of 8-nitroguanosine may contribute to the pathogenesis of inflammation-associated carcinogenesis.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalCancer Letters
Volume262
Issue number2
DOIs
Publication statusPublished - Apr 18 2008
Externally publishedYes

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Keywords

  • 8-Nitroguanosine
  • Abasic site
  • Inflammation
  • Mutation
  • Nitric oxide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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