Phosphorylation of histone H2AX as a measure of radiosensitivity
Phosphorylation of histone H2AX as a measure of radiosensitivity
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DOI：
10.1016/j.ijrobp.2003.09.028
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发表时间：
2004-02-01
影响因子：
7
通讯作者：
Banáth, JP
中科院分区：
文献类型：
--
作者：
Olive, PL;Banáth, JP
目的：组蛋白H2 AX（gammaH 2AX）的磷酸化响应于DNA双链断裂的存在而迅速发生，并且被认为将修复酶募集到这些位点。我们研究了磷酸化H2 AX的表达可以提供关于肿瘤和/或正常组织对辐射敏感性的信息的可能性。方法：使用γ H2 AX抗体染色的单细胞的流式细胞术来测量培养的细胞系、肿瘤细胞和正常组织中的γ H2 AX强度。γ H2 AX在辐射后最初几个小时内的消失速率在更耐辐射的肿瘤和正常细胞系中通常更快，但在C3 H小鼠的放射敏感细胞和正常组织中较慢。一个例外是睾丸，它显示出高背景和快速丢失率。在氧合良好的细胞中，gammaH 2AX的水平至少是缺氧细胞的三倍，产生半最大反应的氧浓度为0.55%。结论：γ H2 AX的表达可作为肿瘤细胞和正常细胞对电离辐射反应的重要信息。(C)2004年爱思唯尔公司
Purpose: Phosphorylation of histone H2AX(gammaH2AX) occurs rapidly in response to the presence of DNA double-strand breaks and is thought to recruit repair enzymes to these sites. We examined the possibility that expression of phosphorylated H2AX could provide information on tumor and/or normal tissue sensitivity to radiation.Methods: Flow cytometry of gammaH2AX antibody-stained single cells was used to measure gammaH2AX intensity in cultured cell lines, tumor cells, and normal tissues.Results: The rate of disappearance of gammaH2AX during the first few hours after irradiation was generally faster in more radioresistant tumor and normal cell lines, but slower in radiosensitive cells and normal tissues from C3H mice. An exception was testis, which showed a high background and rapid loss rate. Levels of gammaH2AX were at least three times higher in well-oxygenated cells than in anoxic cells, and the oxygen concentration that produced a half-maximal response was 0.55%. Hypoxic cells could be detected in SiHa xenografts as a subpopulation with lower expression of gammaH2AX.Conclusions: Analysis of gammaH2AX has the potential to provide useful information on tumor and normal cell response to ionizing radiation after exposure to clinically, relevant doses of radiation. (C) 2004 Elsevier Inc.