title: Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro.
abstract: 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 approximately 80% of all compounds formed) as 8-nitroguanine. Its formation was maximal at approximately 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.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Yermilov
authors.forename: J
authors.initials: J
authors.lastname: Rubio
authors.forename: M
authors.initials: M
authors.lastname: Becchi
authors.forename: M D
authors.initials: MD
authors.lastname: Friesen
authors.forename: B
authors.initials: B
authors.lastname: Pignatelli
authors.forename: H
authors.initials: H
authors.lastname: Ohshima
mesh_terms: D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D006147:Guanine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009566:Nitrates / Q000378:metabolism / Q000633:toxicity*; D009705:Nucleosides / Q000378:metabolism
chemical_list: C095838:8-nitroguanine; D002273:Carcinogens; D009566:Nitrates; D009705:Nucleosides; C039642:peroxynitric acid; D006147:Guanine; D004247:DNA