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 chem...

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Bibliographic Details
Published in:FEBS letters 1995-12, Vol.376 (3), p.207-210
Main Authors: Yermilov, Vladimir, Rubio, Julieta, Ohshima, Hiroshi
Format: Article
Language:English
Subjects:
3-(4-morpholinyl)-sydnone imine
8-Nitroguanine
8-Oxoguanine
Animals
Antioxidants - chemistry
Apurinic Acid - chemistry
Cattle
Deferoxamine - chemistry
DNA - chemistry
DNA damage
electrochemical detector
Free Radicals - chemistry
Guanine - analogs & derivatives
Guanine - chemistry
Nitrates - chemistry
Nitric oxide
nitro8Gua
oxo8Gua
Peroxynitrite
SIN-1
Superoxide
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Summary: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°C ( t 1 2 = ∼4 h ). Peroxynitrite did not increase 8-oxoguanine levels in DNA.
ISSN:0014-5793
1873-3468
DOI:10.1016/0014-5793(95)01281-6