Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.

Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.
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DOI:
10.1371/journal.pone.0025113
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Rothkamm K
Rothkamm K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Horn S;Barnard S;Rothkamm K

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大多数人暴露在电离辐射中是局部的身体暴露。然而,到目前为止,只有有限的工具可用于快速和准确地估计剂量分布和身体免受照射的范围。这些参数对接触者的急诊分诊和临床处理具有重要意义。在这里,用显微镜和流式细胞术测量γ-H_2AX免疫荧光作为全身和局部暴露的快速生物剂量学工具进行了比较。用一个供者的体外均匀X射线照射的血淋巴细胞,在照射后96h的时间点内,生成一个通用的双指数校正函数,用于计算γ-H_2AX焦点/强度产额。对于0.5Gy射线或更高的剂量,焦点--但不是强度--水平在96小时内显著高于本底水平。来自13名志愿者的体外X射线照射血液样本的基于病灶的剂量估计与目标样本的实际剂量非常一致。来自8名志愿者的X-射线照射后血液样本的流式细胞仪剂量估计值与照射后1小时的实际剂量非常吻合,但在照射后24小时的实际剂量较差。在通过混合体外照射和未照射的淋巴细胞模拟的部分身体暴露中,与均匀照射的淋巴细胞相比,焦点/强度分布明显过度分散。对于这两种方法和在所有情况下,使用零污染泊松检验和γ-H_2AX校准函数计算的受照射淋巴细胞的估计比例和该比例的剂量与提供给样品的实际混合比例和剂量非常一致。总之,照射淋巴细胞的γ-H2AX分析可以快速准确地评估全身剂量,而病灶或强度分布的弥散分析有助于确定局部身体剂量和局部暴露情况下的照射部分大小。
Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci – but not intensity – levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.
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发表时间: 2004-01-01
影响因子: 1.7
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