DNA oxidation

DNA oxidation is the process of oxidative damage on Deoxyribonucleic Acid. It occurs most readily at guanine residues due to the high oxidation potential of this base relative to cytosine, thymine, and adenine. It is widely believed to be linked to certain disease and cancers.

More than 20 oxidatively damaged DNA base lesions were identified in 2003 by Cooke et al. and these overlap the 12 oxidized bases reported in 1992 by Dizdaroglu. Two of the most frequently oxidized bases found by Dizdaroglu after ionizing radiation (causing oxidative stress) were the two oxidation products of guanine shown in the Figure. One of these products was 8-OH-Gua (8-hydroxyguanine). (The article 8-Oxo-2'-deoxyguanosine refers to the same damaged base since the keto form 8-oxo-Gua described there may undergo a tautomeric shift to the enol form 8-OH-Gua shown here.) The other product was FapyGua (2,6-diamino-4-hydroxy-5-formamidopyrimidine). Another frequent oxidation product was 5-OH-Hyd (5-hydroxyhydantoin) derived from cytosine.

Most oxidized bases are removed from DNA by enzymes operating within the base excision repair pathway. Removal of oxidized bases in DNA is fairly rapid. For example, 8-oxo-dG was increased 10-fold in the livers of mice subjected to ionizing radiation, but the excess 8-oxo-dG was removed with a half-life of 11 minutes.

Steady-state levels of endogenous DNA damages represent the balance between formation and repair. Swenberg et al. measured average amounts of steady state endogenous DNA damages in mammalian cells. The seven most common damages they found are shown in Table 1. Only one directly oxidized base, 8-hydroxyguanine, at about 2,400 8-OH-G per cell, was among the most frequent DNA damages present in the steady-state.

As reviewed by Valavanidis et al. increased levels of 8-oxo-dG in a tissue can serve as a biomarker of oxidative stress. They also noted that increased levels of 8-oxo-dG are frequently found associated with carcinogenesis and disease.

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