The response of-H2AX in human lymphocytes and lymphocytes subsets measured in whole blood cultures

The response of-H2AX in human lymphocytes and lymphocytes subsets measured in whole blood cultures
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DOI:
10.1080/09553000902781147
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发表时间:
2009-01-01
影响因子:
2.6
通讯作者:
Wilkins, Ruth C.
Wilkins, Ruth C.
中科院分区:
医学3区
文献类型:
--
作者:
Andrievski, Andrei;Wilkins, Ruth C.

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用途:为了评估使用磷酸化组蛋白H2AX蛋白(-H2AX)在人血白细胞作为辐射生物剂量学的快速筛选工具,使用的方法,检查在各种淋巴细胞亚群暴露于辐射后的-H2AX磷酸化的特征。材料与方法:用快速全血流式细胞术分析暴露于0 - 10Gy~(137)Cs照射并培养0 - 48h的人外周血,以测量不同淋巴细胞亚群中的-H_2AX磷酸化。结果如下:淋巴细胞亚群显示出类似的线性剂量反应关系,尽管发现分化簇4+(CD4+)和CD8+淋巴细胞表达的H2AX磷酸化比CD19+淋巴细胞高1.5倍。所有淋巴细胞亚群的磷酸化在1.5小时达到最大值,并在暴露后24小时基本恢复到基线水平。结论:淋巴细胞亚群间-H2AX的表达水平差异很小。该测定法用于辐射生物剂量测定的有用性受到其相对较快的寿命动力学和较大的个体间差异的阻碍。因此,只有在暴露后24小时内获得样本才有意义。即使在这种情况下,该测定也只能用作暴露的指示剂,而不能用作剂量计。
Purpose: To assess the use of phosphorylated histone H2AX protein (-H2AX) in human blood leukocytes as a rapid screening tool for radiation biodosimetry using a method that examines the characteristics of -H2AX phosphorylation in a variety of lymphocyte subsets following exposure to radiation. Materials and methods: Human peripheral blood exposed to 0-10Gy of 137Cs irradiation and cultured for 0-48h was analysed using a rapid whole blood flow cytometry assay to measure -H2AX phosphorylation in different lymphocyte subpopulations. Results: Lymphocyte subsets displayed a similar linear dose response relationship, although cluster of differentiation 4+ (CD4+) and CD8+ lymphocytes were found to express H2AX phosphorylation on the order of 1.5 times higher than CD19+ lymphocytes. Phosphorylation of all lymphocyte subsets reached a maximum at 1.5h and had essentially returned to baseline levels 24h post-exposure. Conclusions: Differences in the expression level of -H2AX between lymphocyte subsets were minimal. The usefulness of this assay for radiation biodosimetry is hampered by its relatively quick lifetime kinetics and large inter-individual variation. Therefore, it could only be useful if samples were obtained within 24h of exposure. Even in this situation, the assay could only be used as an indicator of exposure and not a dosimeter.