M. Whiteman et al., 8-chloroadenine: a novel product formed from hypochlorous acid-induced damage to calf thymus DNA, BIOMARKERS, 4(4), 1999, pp. 303-310
Hypochlorous acid (HOCl) is formed by the action of the enzyme myeloperoxid
ase on hydrogen peroxide and chloride ions. It has been shown to be highly
bactericidal and cytotoxic by a variety of mechanisms, one of which, may be
the modification of DNA. Previously we have demonstrated by GC-MS analysis
that exposure of calf thymus DNA to HOCl causes extensive pyrimidine modif
ication, including 5-chlorocytosine formation. Using GC-MS analysis, we now
demonstrate the formation of an additional chlorinated base product, 8-Cl
adenine. The addition of 50 mu M HOCl was sufficient to produce a significa
nt increase in this product. The reaction of HOCl with adenine in calf thym
us DNA was shown to be rapid with the reaction complete after 1 min, pH-dep
endence studies suggest HOCl rather than its conjugate base (OCl-) to be re
sponsible for 8-Cl adenine formation. Other commercially available chlorina
ted base products, 6-Cl guanine or 2-Cl adenine were not detected. Therefor
e, 8-Cl adenine might prove a useful biomarker for studying the role of rea
ctive chlorine species (RCS) during inflammatory processes.