Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells.
Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells.
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DOI：
10.1042/bj20071643
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发表时间：
2008-07-01
期刊：
影响因子：
--
通讯作者：
Spitz DR
中科院分区：
文献类型：
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作者：
Dayal D;Martin SM;Limoli CL;Spitz DR
慢性氧化应激与暴露于电离辐射（IR）后的基因组不稳定有关。然而，缺乏显示特定活性氧与 IR 诱导突变表型之间直接因果关系的数据。目前的研究表明，IR 诱导的基因组不稳定细胞（其特征是染色体不稳定以及突变和基因扩增频率增加）的稳态过氧化氢水平增加了 3 倍，但超氧化物水平没有增加。此外，从平行研究中分离出的稳定克隆显示过氧化氢酶和谷胱甘肽过氧化物酶活性显着增加。用聚乙二醇缀合过氧化氢酶[PEG-CAT]处理不稳定细胞，以剂量依赖性方式降低突变频率和突变率。此外，使用3-氨基三唑抑制稳定克隆中的过氧化氢酶活性增加了突变频率和率。这些结果清楚地证明了过氧化氢介导的慢性氧化应激与哺乳动物细胞暴露于红外线后持续许多代的突变表型之间的因果关系。
Chronic oxidative stress has been associated with genomic instability following exposure to ionizing radiation (IR). However, data showing direct causal linkages between specific reactive oxygen species and the IR-induced mutator phenotype are lacking. The current study demonstrates that IR-induced genomically unstable cells (characterized by chromosomal instability and increased mutation and gene amplification frequencies) show a 3-fold increase in steady-state levels of hydrogen peroxide, but not superoxide. Furthermore, stable clones isolated from parallel studies showed significant increases in catalase and glutathione-peroxidase activity. Treatment of unstable cells with polyethylene glycol-conjugated catalase [PEG-CAT] reduced the mutation frequency and mutation rate in a dose dependent fashion. In addition, inhibiting catalase activity in the stable clones using 3-aminotriazole increased mutation frequency and rate. These results clearly demonstrate the causal relationship between chronic oxidative stress mediated by hydrogen peroxide and the mutator phenotype that persists many generations following exposure of mammalian cells to IR.