Kim Ja-Eun, Chung Myung-Hee
Seoul National University College of Medicine, Department of Pharmacology, South Korea.
Free Radic Res. 2006 May;40(5):461-6. doi: 10.1080/10715760600570539.
8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), the most common oxidatively modified nucleoside, is released from oxidized DNA and oxidized nucleotide pool. However, little information is available regarding the metabolic pathway of free 8-oxo-dG. In this study, we generated radiolabeled 8-oxo-dG to track its metabolic fate. We report that 8-oxo-dG is neither phosphorylated to 8-oxo-dGMP nor degraded to the free base, 8-oxo-7,8-dihydroguanine (8-oxo-Gua), indicating that 8-oxo-dG is not a substrate for nucleotide synthesis. This result was confirmed by the finding that no radioactivity was detected in the DNA of U937 cells after incubating the cells with radiolabeled 8-oxo-dG. These observations indicate that 8-oxo-dG produced by oxidative stress is not reutilized for DNA synthesis.
8-氧代-7,8-二氢-2'-脱氧鸟苷(8-氧代-dG)是最常见的氧化修饰核苷,它从氧化的DNA和氧化的核苷酸池中释放出来。然而,关于游离8-氧代-dG的代谢途径,目前所知甚少。在本研究中,我们生成了放射性标记的8-氧代-dG以追踪其代谢命运。我们报告称,8-氧代-dG既不磷酸化为8-氧代-dGMP,也不降解为游离碱8-氧代-7,8-二氢鸟嘌呤(8-氧代-Gua),这表明8-氧代-dG不是核苷酸合成的底物。用放射性标记的8-氧代-dG孵育U937细胞后,在其DNA中未检测到放射性,这一发现证实了该结果。这些观察结果表明,氧化应激产生的8-氧代-dG不会被重新用于DNA合成。