Cardozo-Pelaez F, Brooks P J, Stedeford T, Song S, Sanchez-Ramos J
James Haley Veterans Affairs Research Service, Tampa, FL, USA.
Free Radic Biol Med. 2000 Mar 1;28(5):779-85. doi: 10.1016/s0891-5849(00)00172-6.
8-Hydroxy-2'-deoxyguanosine (oxo(8)dG) has been used as a marker of free radical damage to DNA and has been shown to accumulate during aging. Oxidative stress affects some brain regions more than others as demonstrated by regional differences in steady state oxo(8)dG levels in mouse brain. In our study, 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 such as the cerebellum, cortex, and pons 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 activities of antioxidant enzymes (Cu/Zn superoxide dismutase, mitochondrial superoxide dismutase, and glutathione peroxidase) and the levels of the endogenous antioxidant glutathione are not predictors of the degree of free radical induced damage to DNA in different brain regions. Although each brain region has significant differences in antioxidant defenses, the capacity to excise the oxidized base from DNA seems to be the major determinant of the steady state levels of oxo(8)dG in each brain region.
8-羟基-2'-脱氧鸟苷（oxo(8)dG）已被用作DNA自由基损伤的标志物，并且已证实在衰老过程中会累积。氧化应激对某些脑区的影响大于其他脑区，小鼠脑中稳态oxo(8)dG水平的区域差异证明了这一点。在我们的研究中，我们发现中脑、尾状核壳核和海马体等区域在总DNA中显示出高水平的oxo(8)dG，而小脑、皮层、脑桥和延髓等区域的水平较低。DNA损伤基础水平的这些区域差异与从DNA中去除oxo(8)dG的区域能力呈负相关。此外，抗氧化酶（铜/锌超氧化物歧化酶、线粒体超氧化物歧化酶和谷胱甘肽过氧化物酶）的活性以及内源性抗氧化剂谷胱甘肽的水平并不是不同脑区自由基诱导的DNA损伤程度的预测指标。尽管每个脑区在抗氧化防御方面存在显著差异，但从DNA中切除氧化碱基的能力似乎是每个脑区oxo(8)dG稳态水平的主要决定因素。
