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

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 microM) for 1h 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.

• Authors: Kazuyoshi Kaneko, Teruo Akuta, Tomohiro Sawa, Ha Won Kim, Shigemoto Fujii, Tatsuya Okamoto, Hitoshi Nakayama, Hajime Ohigashi, Akira Murakami, Takaaki Akaike
• Journal: Cancer letters (Cancer Lett) Vol. 262 Issue 2 Pg. 239-47 (Apr 18 2008) ISSN: 0304-3835 [Print] Ireland
• PMID: 18248787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 8-nitroguanosine
• Mutagens
• Nitro Compounds
• Nitrogen Oxides
• Guanosine
• Transferases (Other Substituted Phosphate Groups)
• UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase

Topics

• Animals
• CHO Cells
• Cricetinae
• Cricetulus
• DNA Damage
• Guanosine (analogs & derivatives, toxicity)
• Mutagenicity Tests
• Mutagens (toxicity)
• Nitro Compounds (toxicity)
• Nitrogen Oxides (metabolism)
• Transferases (Other Substituted Phosphate Groups) (genetics)