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 nitrit e (NO2-) accumulation. Activated phagocytes release myeloperoxidase generat ing 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 25 0 mu M) at pH 7.4 did not induce oxidative DNA base damage. However, incuba tion of DNA with NO2- in the presence of HOCl led to increases in thymine g lycol, 5-hydroxyhydantoin, 8-hydroxyadenine and 5-chlorouracil to levels hi gher than those achieved by HOCl alone. No significant increases in 8-hydro xyguanine, xanthine, hypoxanthine, 2-hydroxyadenine, FAPy guanine, FAPy ade nine and 8-chloroadenine were observed. HOCl-induced depletion of FAS guani ne and 8-hydroxyguanine was reduced in the presence of NO2-. Modification o f DNA by HOCl/NO2- (presumably generating NO2Cl) produces a pattern of DNA base damage products in isolated DNA that is similar to the pattern produce d by HOCl but not other reactive species. (C) 1999 Academic Press.