Mechanisms of free radical-induced damage to DNA

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. Hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to adduct radicals, further reactions of which yield numerous products. These include DNA base and sugar products, single- and double-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. There is 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.

Keywords::

• free radicals
• hydroxyl radical
• hydrated electron
• hydrogen atom
• mechanisms of product formation
• DNA base damage
• DNA sugar damage
• tandem lesions
• clustered lesions
• DNA-protein cross-links

Acknowledgement

Some of the figures in this article were adapted from original papers. Appropriate references related to those figures were given in the text.

Declaration of interest The authors report no conflicts of interests. The authors alone are responsible for the content and writing of the paper.