Nitro-Tyrosine as Promoter of Free Radical Damage in a DNA Model System

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Abstract
Nitro-tyrosine considerably promotes the degradation of DNA, when incubated with Cu2+ and ascorbate in oxygenated aqueous solution. This deleterious process requires oxygen and can be inhibited with catalase, indicating that H2O2 is involved, via the reduction of oxygen. Menadione and 2,4,6-trinitro-benzenesulfonate, known to catalyze particularly fast such reduction of oxygen, were only slightly more active than nitro-tyrosine. Degradation of DNA can be explained by a site-specific Fenton type reaction of H2O2 with the DNA-Cu+ complex. DNA-Cu+ + H2O2 → DNA' ' 'OH + Cu2+ + OH− Copper-chelating agents (EDTA and penicillamine) prevent DNA degradation, whereas OH-scavengers (t-butanol) are ineffective. The deleterious activity of nitro-tyrosine (and of other nitroaromatics) in the DNA model system may indicate important toxicological implications, since aromatic nitration is a significant mode of action of nitrogen dioxide.