Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro

Nitric oxide and superoxide anion, both formed in inflamed tissues, react rapidly to form the peroxynitrite anion (ONOO−), a strong oxidant which can initiate reactions characteristic of hydroxyl radical (HO•), nitronium ion (NO2+) and nitrogen dioxide radical (NO2•). Peroxynitrite, therefore, may c...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1995-09, Vol.16 (9), p.2045-2050
Main Authors: Yermilov, Vladimir, Rubio, Julieta, Becchi, Michel, Friesen, Marlin D., Pignatelli, Brigitte, Ohshima, Hiroshi
Format: Article
Language:English
Subjects:
Biochemistry, Molecular Biology
Biological and medical sciences
Carcinogens - metabolism
Carcinogens - toxicity
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
DNA - drug effects
DNA - metabolism
DNA Damage
Fundamental and applied biological sciences. Psychology
Guanine - analogs & derivatives
Guanine - biosynthesis
Guanine - metabolism
Hydrogen-Ion Concentration
Kinetics
Life Sciences
Molecular and cellular biology
Nitrates - metabolism
Nitrates - toxicity
Nucleosides - metabolism
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Summary:Nitric oxide and superoxide anion, both formed in inflamed tissues, react rapidly to form the peroxynitrite anion (ONOO−), a strong oxidant which can initiate reactions characteristic of hydroxyl radical (HO•), nitronium ion (NO2+) and nitrogen dioxide radical (NO2•). Peroxynitrite, therefore, may cause DNA or tissue damage, contributing to the multistage carcinogenesis process. We have studied reactions of various bases, nucleosides or deoxynucleosides with peroxynitrite in vitro. Guanine reacted rapidly with peroxynitrite under physiological conditions and formed several substances, two of which were yellow, a characteristic of nitro and nitroso compounds. On the basis of chromatographic and spectral evidence we identified the major compound (which accounts for ∼80% of all compounds formed) as 8-nitroguanine. Its formation was maximal at ∼pH 8 and increased dose-dependently with peroxynitrite concentration, but was not dependent on guanine concentration. The presence of ferric ions, which has been shown to catalyse nitration of tyrosine, did not affect nitration of guanine. 8-Nitroguanine could act as a specific marker for DNA damage induced by peroxynitrite in inflamed tissues.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/16.9.2045