Graduate School, Wenzhou Medical College, University Town, Wenzhou, Zhejiang 325035, China.
Oxid Med Cell Longev. 2013;2013:303181. doi: 10.1155/2013/303181. Epub 2013 Apr 29.
The relationship between the oxidative damage of nucleic acids and aging of animals was investigated by analyzing the nucleic acids derived from various tissue specimens of naturally aged Sprague-Dawley (SD) rats. For this purpose, we established an accurate and sensitive isotope-diluted LC-MS/MS method to determine the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn) in DNA and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in RNA. An age-dependent increase in oxidative DNA and RNA damage was observed in the various organs examined, including the brain, liver, kidneys, and testes. Similar increases in the 8-oxo-dGsn and 8-oxo-Gsn contents were observed in three parts of the brain, the hippocampus, cerebral cortex, and cerebellum, among which, the values for the hippocampus were always the highest. When the oxidized guanosine metabolites were quantified with urine, a similar age-dependent increase was observed for both 8-oxo-dGsn and 8-oxo-Gsn. However, unlike the results of nucleic acid samples derived from the tissues, the amount of 8-oxo-Gsn was significantly higher compared to that of 8-oxo-dGsn, probably reflecting the fact that RNA degradation occurs more frequently than DNA degradation. Our finding indicates that the amount of urinary 8-oxo-Gsn could be considered as a biomarker for the sensitive measurement of oxidative stress and aging.
本研究通过分析自然衰老 Sprague-Dawley（SD）大鼠不同组织标本中的核酸，探讨了核酸的氧化损伤与动物衰老之间的关系。为此，我们建立了一种准确、灵敏的同位素稀释 LC-MS/MS 方法，用于测定 DNA 中 8-氧代-7,8-二氢-2'-脱氧鸟苷（8-氧代-dGsn）和 RNA 中 8-氧代-7,8-二氢鸟苷（8-氧代-Gsn）的水平。在检测的各种器官中，包括大脑、肝脏、肾脏和睾丸，均观察到氧化 DNA 和 RNA 损伤随年龄的增长而增加。在大脑的三个部分（海马体、大脑皮层和小脑）中观察到 8-氧代-dGsn 和 8-氧代-Gsn 含量的相似增加，其中海马体的值始终最高。当用尿液定量氧化鸟嘌呤代谢物时，观察到 8-氧代-dGsn 和 8-氧代-Gsn 均随年龄的增长而增加。然而，与组织样本核酸的结果不同，8-氧代-Gsn 的量明显高于 8-氧代-dGsn，这可能反映了 RNA 降解比 DNA 降解更频繁的事实。我们的发现表明，尿中 8-氧代-Gsn 的含量可作为衡量氧化应激和衰老的敏感生物标志物。
