Possible Mechanisms of DNA Damage Induced by Oxidative Stress

Possible Mechanisms of DNA Damage Induced by Oxidative Stress 

It has been known for many years that neither Oa nor H2O2 causes any strand breakage in DNA, if the reaction mixture is carefully freed of transition metal ions (see e.g. Rowley and Halliwell, 1983). Our later work 

A second explanation of the ability of oxidative stress to cause DNA damage is that the stress tri ers a series of metabolic events within the cell that lead to activation of nuclease enzymes, which cleave the DNA backbone. Oxidative stress causes rises in intracellular free Ca, which can fiagment DNA by activating Ca -dependent endonucleases (Orrenius etal., 1989 Farber, 1990 Ueda and Shah, 1992) in a mechanism with some of the features of apoptosis (see Wyllie, 1980). An example of apoptosis is the killing of immature thymocytes by glucocorticoid hormones, which activate a cell-destructive process that apparently involves DNA fragmentation by a Ca -dependent nuclease. 

These two mechanisms (DNA damage by OH or by activation of nucleases) are not mutually exclusive, i.e. they could both take place (Fig. 13.1). Indeed, there is evidence consistent with the existence of both mechanisms. Their relative importance may depend on the cell type used and on how the oxidative stress is imposed (Halliwell and Aruoma, 1991). For example, chelating agents that bind iron ions into chelates unable to generate OH (such as desferrioxamine. 

Strand Breakage DNA Base Modification Deoxyribose Fragmentation 

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