DNA damage, repair, and antioxidant systems in brain regions: A correlative study

8-Hydroxy-2'-deoxyguanosine (oxo(8)dG) has been used as a marker of free ra dical damage to DNA and has been shown to accumulate during aging. Oxidativ e stress affects some brain regions more than others as demonstrated by reg ional differences in steady state oxo(8)dG levels in mouse brain. In our st udy, we have shown that regions such as the midbrain, caudate putamen, and hippocampus show high levels of oxo(8)dG in total DNA, although regions suc h as the cerebellum, cortex, and pens and medulla have lower levels. These regional differences in basal levels of DNA damage inversely correlate with the regional capacity to remove oxo(8)dG from DNA. Additionally, the activ ities of antioxidant enzymes (Cu/Zn superoxide dismutase, mitochondrial sup eroxide dismutase, and glutathione peroxidase) and the levels of the endoge nous antioxidant glutathione are not predictors of the degree of free radic al induced damage to DNA in different brain regions. Although each brain re gion has significant differences in antioxidant defenses, the capacity to e xcise the oxidized base from DNA seems to be the major determinant of the s teady state levels of oxo(8)dG in each brain region.