Formation of 8-nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination.
Peroxynitrite is a strong oxidant formed by reaction of nitric oxide with superoxide in inflamed tissues. We have demonstrated that 8-nitroguanine is formed dose-dependently in calf thymus DNA incubated with low concentrations of peroxynitrite in vitro. 8-Nitroguanine in acid-hydrolyzed DNA was chemically reduced into 8-aminoguanine, which was analyzed using high performance liquid chromatography with electrochemical detection. Only peroxynitrite, but not nitrite, tetranitromethane nor NO-releasing compounds, formed 8-nitroguanine. Antioxidants and desferrioxamine inhibited the reaction. 8-Nitroguanine was depurinated from DNA incubated at pH 7.4, 37 degrees C (t1/2 = approximately 4 h). Peroxynitrite did not increase 8-oxoguanine levels in DNA.
D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001080:Apurinic Acid / Q000737:chemistry*; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D003676:Deferoxamine / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D009566:Nitrates / Q000737:chemistry*
C095838:8-nitroguanine; D000975:Antioxidants; D005609:Free Radicals; D009566:Nitrates; D001080:Apurinic Acid; C039642:peroxynitric acid; D006147:Guanine; D004247:DNA; D003676:Deferoxamine