TY - JOUR
T1 - Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro
AU - Yermilov, Vladimir
AU - Rubio, Julieta
AU - Becchi, Michel
AU - Friesen, Marlin D.
AU - Pignatelli, Brigitte
AU - Ohshima, Hiroshi
N1 - Funding Information:
The authors would like to thank Dr J.Cheney for editing the manuscript and Mrs E.Bayle for her much appreciated secretarial work. VY and JR are recipients of a European Science Foundation fellowship and a Universidad Nacional Autonoma de Mexico Scholarship respectively.
PY - 1995/9
Y1 - 1995/9
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/16.9.2045
DO - 10.1093/carcin/16.9.2045
M3 - Article
C2 - 7554052
AN - SCOPUS:0029135397
SN - 0143-3334
VL - 16
SP - 2045
EP - 2050
JO - Carcinogenesis
JF - Carcinogenesis
IS - 9
ER -