Developing Gender-Specific Gene Expression Biodosimetry Using a Panel of Radiation-Responsive Genes for Determining Radiation Dose in Human Peripheral Blood
Developing Gender-Specific Gene Expression Biodosimetry Using a Panel of Radiation-Responsive Genes for Determining Radiation Dose in Human Peripheral Blood
复制标题
使用一组辐射响应基因开发性别特异性基因表达生物剂量测定法，以确定人外周血中的辐射剂量
DOI：
10.1667/rr15355.1
复制
发表时间：
2019-10-01
影响因子：
3.4
通讯作者：
Liu, Qing-Jie
中科院分区：
文献类型：
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作者：
Li, Shuang;Lu, Xue;Liu, Qing-Jie
在大规模放射事件中，需要快速和高通量的生物剂量测定。基于基因表达的生物剂量测定法是一种很有前途的方法来确定辐射照射后的剂量。我们之前在系统回顾的基础上确定了35个候选基因作为生物剂量学标记。本研究的目的是建立并验证一种基于特定基因表达的放射生物剂量测定法，该方法使用一组人类外周血中高度放射反应的基因，以提高剂量估计的准确性。用Co-60 γ射线以1 Gy/min的剂量率照射0、0.5、1、2、3、4、6和8 Gy的人类外周血样本。我们使用实时聚合酶链反应（qRT-PCR）检测了候选基因在放疗后6、12、24和48小时的表达模式。采用逐步回归分析建立各时间点基于基因表达的剂量学模型。另外10名健康供体（盲体样本）和4名全身辐照（TBI）患者的样本用于验证辐射剂量学模型。我们观察到人外周血CDKN1A、BAX、MDM2、XPC、PCNA、FDXR、GDF-15、DDB2、TNFRSF10B、PHPT1、ASTN2、RPS27L、BBC3、TNFSF4、POLH、CCNG1、PPM1D和GADD45A在不同时间点呈显著的线性剂量效应关系。然而，这些基因的表达水平受到个体间变异和性别的影响。我们发现，性别相关回归模型可以解释辐射后24 h 0.85的方差，也可以准确地估计出0-5 Gy剂量范围内的人体外周血液样本和TBI患者的吸收辐射剂量。本研究表明，基于一组高放射性反应基因开发性别特异性生物剂量测定法可能有助于推进基因表达特征在放射事故或临床治疗中剂量估计的应用。(C) 2019年由辐射研究学会主办
In a large-scale radiological incident, rapid and high-throughput biodosimetry would be needed. Gene expression-based biodosimetry is a promising approach to determine the dose received after radiation exposure. We previously identified 35 candidate genes as biodosimetry markers based on a systematic review. The goal of the current study was to establish and validate a specific gene expression-based radiological biodosimetry using a panel of highly radio-responsive genes in human peripheral blood for improving the accuracy of dose estimation. Human peripheral blood samples from 30 adult donors were irradiated to 0, 0.5, 1, 2, 3, 4, 6 and 8 Gy with Co-60 gamma rays at a dose rate of 1 Gy/min. We examined the expression patterns of candidate genes using real-time polymerase chain reaction (qRT-PCR) at 6, 12, 24 and 48 h postirradiation. Stepwise regression analysis was employed to develop the gene expression-based dosimetry models at each time point. Samples from another 10 healthy donors (blind samples) and four total-body irradiated (TBI) patients were used to validate the radiation dosimetry models. We observed significant linear dose-response relationships of CDKN1A, BAX, MDM2, XPC, PCNA, FDXR, GDF-15, DDB2, TNFRSF10B, PHPT1, ASTN2, RPS27L, BBC3, TNFSF4, POLH, CCNG1, PPM1D and GADD45A in human peripheral blood at the various time points. However, the expression levels of these genes were affected by interindividual variations and gender. We found that the genderdependent regression models could explain 0.85 of variance at 24 h postirradiation and could also accurately estimate the absorbed radiation doses with dose range of 0-5 Gy, in human peripheral blood samples irradiated ex vivo and from TBI patients, respectively. This study demonstrates that developing gender-specific biodosimetry based on a panel of highly radioresponsive genes may help advance the application of gene expression signature for dose estimation in the event of a radiological accident or in clinical treatment. (C) 2019 by Radiation Research Society