Nitro-tyrosine as promoter of free radical damage in a DNA model system.

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-trinitrobenzenesulfonate, 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.