Abstract
Activated phagocytes generate a complex mixture of oxidants that are believed to be crucial to bacterial cell killing. However, excessive or misplaced generation of these oxidants is known to damage host tissue. This damage is understood to be important in a number of diseases, and considerble evidence has accumulated for a link between chronic inflammation and some cancers. This is believed to occur through a variety of mechanisms, including direct damage to DNA, that can lead to mutation, and damage to enzymes, which are responsible for the synthesis and repair of DNA. In this chapter we discuss the nature and properties of oxidants [e.g., hypochlorous acid (HOCl), nitric oxide (NO) and peroxynitrite (ONOO−)] generated by activated phagocytes, and further reactive species [e.g., hydroxyl radicals (HO•), nitrogen dioxide (•NO2), nitrosoperoxycarbonate (ONOOCO2 −), nitrosyl chloride (NO2Cl)] that are generated from their interactions in vivo. We focus on the reactions of these species that lead to chlorination and nitration of DNA and related nucleic acid components and examine the structural and functional consequences of these reactions. We also discuss the merits and shortcomings of using these chlorinated and nitrated DNA products as potential biomarkers of disease.
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Hawkins, C.L., Pattison, D.I., Whiteman, M., Davies, M.J. (2007). Chlorination and Nitration of DNA and Nucleic Acid Components. In: Evans, M.D., Cooke, M.S. (eds) Oxidative Damage to Nucleic Acids. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72974-9_2
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