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|Author(s):||M Miral Dizdar; Pawel Jaruga;|
|Title:||Mechanisms of free radical-induced damage to DNA|
|Published:||April 01, 2012|
|Abstract:||Endogenous and exogenous sources cause free radical-induced DNA damage in living organisms by a variety of mechanisms. The highly reactive hydroxyl radical reacts with the heterocyclic DNA bases and the sugar moiety near or at diffusion-controlled rates by addition to the double bonds and H atom-abstraction from the C‹H-bonds of the sugar moiety and the methyl group of thymine. Ionizing radiation-generated hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to OH‹ or H‹adduct radicals and radical anions of DNA bases, the allyl radical of thymine and the C‹centered radicals of the sugar moiety. Further reactions of these radicals yield a plethora of products. These include DNA base and sugar products, single- and double-strand strand breaks, 8,5'-cyclopurine-2'-deoxynucleosides, tandem lesions, clustered sites and DNA-protein cross-links. Reaction conditions and the presence or absence of oxygen profoundly affect the types and yields of the products. Tandem lesions consist of two adjacent damaged bases on the same strand, and covalent cross-links between two adjacent bases on the same strand or two bases on the opposing strands. Clustered lesions are produced almost exclusively by ionizing radiations and can be tandem on the same strand or on opposite strands within one or two helical turns of DNA and are distinct from double-strand breaks. DNA base radicals add to the aromatic ring of amino acids generating covalent DNA-protein cross-links in mammalian chromatin. The combination of a DNA base radical and an amino acid radical can also produce such cross-links. There is a mounting evidence for an important role of free radical-induced DNA damage in the etiology of numerous diseases including cancer. Further understanding of mechanisms of free radical-induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importance for disease prevention and treatment.|
|Citation:||Free Radical Research|
|Pages:||pp. 382 - 419|
|Keywords:||Cancer, DNA damage and repair, DNA repair defects, Cancer biomarkers|
|DOI:||http://dx.doi.org/10.3109/10715762.2011.653969 (Note: May link to a non-U.S. Government webpage)|
|PDF version:||Click here to retrieve PDF version of paper (2MB)|