8-Chloroadenine: a novel product formed from hypochlorous acid-induced damage to calf thymus DNA |
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Authors: | MATTHEW WHITEMAN ANDREW JENNER BARRY HALLIWELL |
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Institution: | 1. International Antioxidant Research Centre, Pharmacology Group, University of
London, Kings College, Manresa Road, London, SW3 6LX, UK;2. Department of Biochemistry, National University of Singapore, 10 Kent Ridge
Crescent, Singapore, 119260 |
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Abstract: | Hypochlorous acid (HOCl) is formed by the action of the enzyme myeloperoxidase 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 modification, 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 μM HOCl was sufficient to produce a significant increase in this product. The reaction of HOCl with adenine in calf thymus DNA was shown to be rapid with the reaction complete after 1 min. pH-dependence studies suggest HOCl rather than its conjugate base (OCl-) to be responsible for 8-Cl adenine formation. Other commercially available chlorinated base products, 6-Cl guanine or 2-Cl adenine were not detected. Therefore, 8-Cl adenine might prove a useful biomarker for studying the role of reactive chlorine species (RCS) during inflammatory processes. |
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Keywords: | Hypochlorous Acid Reactive Chlorine Species 8-chloroadenine Inflammation Oxidative Dna Damage |
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