The Nucleotide Pool, a Target for Low-Dose γ-Ray-Induced Oxidative Stress
The Nucleotide Pool, a Target for Low-Dose γ-Ray-Induced Oxidative Stress
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DOI：
10.1667/rr1399.1
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发表时间：
2008-12-01
影响因子：
3.4
通讯作者：
Haghdoost, Siamak
中科院分区：
文献类型：
--
作者：
Sangsliwan, Traimate;Haghdoost, Siamak
当活性氧(ROS)的生成超过细胞的抗氧化能力时，就会发生氧化应激。过量的ROS与细胞成分反应并修改细胞成分核酸修饰是主要感兴趣的，因为它们可能导致突变。8-氧代-7，8-二氢-2-脱氧鸟苷(8-oxo-DG)是一种由DNA中的ROS和核苷酸池中的ROS形成的致突变损伤。8-oxo-DG通过碱基切除修复从DNA中移除，并通过核苷酸净化酶hMTH1从核苷酸池中移除。HMTH1将8-oxo-dGTP水解为8-oxo-dGMP，释放到细胞外环境中，可作为氧化应激的标志。本工作的目的是在人全血、人成纤维细胞和刺激淋巴细胞三种细胞模型体系中，建立辐射诱导的细胞外8-oxo-dG和hMTH1在mGy射线范围内的剂量-反应关系。细胞外8-oxo-dG用ELISA法检测，hMTH-1用Western blotting检测。我们的结果表明，低剂量电离辐射诱导了应激反应，导致细胞外8-oxo-dG的形成和hMTH1的诱导。这表明核苷酸池是辐射诱导应激反应的重要靶点。(C)2008年，由辐射研究学会提供
Oxidative stress occurs when the generation of reactive oxygen species (ROS) exceeds the cellular antioxidant capacity. The excess ROS react with and modify cellular components Nucleic acid modifications are of principal interest because they may cause mutations. 8-Oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dG) is a mutagenic lesion that can be formed by ROS in DNA as well as in the nucleotide pool. 8-Oxo-dG is removed from the DNA by base excision repair and from the nucleotide pool by the nucleotide sanitization enzyme hMTH1. hMTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, which is released to the extracellular environment and can serve as a marker of oxidative stress. The aim of this work was to establish the dose-response relationship for radiation-induced extracellular 8-oxo-dG and hMTH1 in the mGy range of gamma rays in three cellular model systems: human whole blood, human fibroblasts and stimulated lymphocytes. Extracellular 8-oxo-dG was analyzed with the use of an ELISA and hMTH 1 by Western blotting. Our results demonstrate that low-dose ionizing radiation induces a stress response that leads to the formation of extracellular 8-oxo-dG and induction of hMTH 1 in all three cellular model systems tested. This suggests that the nucleotide pool is an important target for radiation-induced stress response. (C) 2008 by Radiation Research Society