Hypochlorous acid induced DNA base modification: Potentiation by nitrite: Biomarkers of DNA damage by reactive oxygen species

Chronic inflammation results in increased nitric oxide formation and nitrite (NO2-) accumulation. Activated phagocytes release myeloperoxidase generating the cytotoxic agent hypochlorous acid (HOCl), Reaction of HOCl with NO2- results in the formation of nitryl chloride (NO2Cl), a potent oxidising, nitrating and chlorinating species. Exposure of DNA to NO2- alone (up to 250 mu M) at pH 7.4 did not induce oxidative DNA base damage. However, incubation of DNA with NO2- in the presence of HOCl led to increases in thymine glycol, 5-hydroxyhydantoin, 8-hydroxyadenine and 5-chlorouracil to levels higher than those achieved by HOCl alone. No significant increases in 8-hydroxyguanine, xanthine, hypoxanthine, 2-hydroxyadenine, FAPy guanine, FAPy adenine and 8-chloroadenine were observed. HOCl-induced depletion of FAS guanine and 8-hydroxyguanine was reduced in the presence of NO2-. Modification of DNA by HOCl/NO2- (presumably generating NO2Cl) produces a pattern of DNA base damage products in isolated DNA that is similar to the pattern produced by HOCl but not other reactive species. (C) 1999 Academic Press.