Biological and dietary antioxidants protect against DNA nitration induced by reaction of hypochlorous acid with nitrite

Nitryl chloride, formed by reaction of hypochlorous acid with nitrite, might contribute to nitrative damage of biomolecules in addition to peroxynitrite. Damage of DNA by these reactive nitrogen oxide species is implicated in carcinogenesis associated with chronic infections and inflammation. Nitrated DNA adducts, such as 8-nitroguanine and 8-nitroxanthine, are not stable in DNA since they undergo spontaneous depurination, leading to apurinic site formation. In this report, we investigate the protective effect of biological and dietary antioxidants in inhibiting DNA nitration induced by nitryl chloride. The effect of inhibition was evaluated by decrease of 8-nitroxanthine and 8-nitroguanine formation. Among the 21 compounds examined, dihydrolipoic acid is the most effective in preventing DNA nitration, followed by N-acetyl-l-cysteine and folic acid. For sulfur-containing compounds, the more highly reduced compounds are stronger inhibitors of DNA nitration. The major product of N-acetyl-l-cysteine reaction with nitryl chloride is characterized as the (R)-2-acetylamino-3-sulfopropionic acid, a physiologically irreversible product, suggesting that nitryl chloride is a strong oxidizing agent.