Te Koppele J M, Lucassen P J, Sakkee A N, Van Asten J G, Ravid R, Swaab D F, Van Bezooijen C F
TNO Prevention and Health, Division of Vascular and Connective Tissue Research, Gaubius Laboratory, Leiden, The Netherlands.
Neurobiol Aging. 1996 Nov-Dec;17(6):819-26. doi: 10.1016/s0197-4580(96)00165-0.
Accumulation of oxidative DNA damage has been proposed to underlie aging and neurodegenerative diseases such as Alzheimer's Disease (AD). The DNA adduct 8-hydroxy-2'-deoxyguanosine (8OHdG) is considered a good indicator of oxidative DNA damage. To investigate whether this type of DNA damage is involved in AD etiology, 8OHdG levels were determined in postmortem human brain tissue of controls and AD patients (in frontal, occipital, and temporal cortex and in hippocampal tissue). Parametric studies in rat revealed no influences of postmortem delay, repeated freezing/thawing or storage time. In human brain, approximately two 8OHdG molecules were present per 10(5) 2'-deoxyguanosines. In AD patients and controls, 8OHdG-levels were not related to age, sex, or brain region. Also, no differences were found between controls and AD patients. It was concluded that 8OHdG in nuclear DNA, although present throughout the brain in fairly high amounts, does not accumulate with age, nor does it appear to be involved in AD. More detailed studies are required to extend this conclusion to other types of oxidative damage.
氧化DNA损伤的积累被认为是衰老和神经退行性疾病（如阿尔茨海默病，AD）的基础。DNA加合物8-羟基-2'-脱氧鸟苷（8OHdG）被视为氧化DNA损伤的良好指标。为了研究这种类型的DNA损伤是否与AD病因有关，对对照组和AD患者（额叶、枕叶和颞叶皮质以及海马组织）的死后人类脑组织中的8OHdG水平进行了测定。对大鼠的参数研究表明，死后延迟、反复冻融或储存时间均无影响。在人类大脑中，每10(5)个2'-脱氧鸟苷中约有两个8OHdG分子。在AD患者和对照组中，8OHdG水平与年龄、性别或脑区无关。此外，对照组和AD患者之间未发现差异。得出的结论是，核DNA中的8OHdG虽然在整个大脑中含量相当高，但不会随年龄积累，也似乎与AD无关。需要更详细的研究将这一结论扩展到其他类型的氧化损伤。
