Center for Radiological Research, Columbia University Medical Center, New York, New York 10032.
Radiat Res. 2013 Dec;180(6):575-83. doi: 10.1667/RR13343.1. Epub 2013 Oct 29.
We report a large-scale reduced expression of genes in pathways related to cell-type specific immunity functions that emerges from microarray analysis 48 h after ex vivo γ-ray irradiation (0, 0.5, 2, 5, 8 Gy) of human peripheral blood from five donors. This response is similar to that seen in patients at 24 h after the start of total-body irradiation and strengthens the rationale for the ex vivo model as an adjunct to human in vivo studies. The most marked response was in genes associated with natural killer (NK) cell immune functions, reflecting a relative loss of NK cells from the population. T- and B-cell mediated immunity genes were also significantly represented in the radiation response. Combined with our previous studies, a single gene expression signature was able to predict radiation dose range with 97% accuracy at times from 6-48 h after exposure. Gene expression signatures that may report on the loss or functional deactivation of blood cell subpopulations after radiation exposure may be particularly useful both for triage biodosimetry and for monitoring the effect of radiation mitigating treatments.
我们报告了一项大规模的基因表达下调,这些基因与细胞类型特异性免疫功能相关的途径有关,这是从五个供体的外周血在体外接受γ射线照射(0、0.5、2、5、8 Gy)48 小时后的微阵列分析中得出的。这种反应类似于全身照射开始后 24 小时患者的反应,这增强了体外模型作为人类体内研究的辅助手段的合理性。最显著的反应是与自然杀伤(NK)细胞免疫功能相关的基因,反映了 NK 细胞从群体中相对缺失。T 细胞和 B 细胞介导的免疫基因也在辐射反应中显著表达。结合我们之前的研究,在暴露后 6-48 小时的时间内,单一的基因表达特征能够以 97%的准确率预测辐射剂量范围。在辐射暴露后可能报告血细胞亚群丢失或功能失活的基因表达特征,对于生物剂量测定的分类和监测辐射缓解治疗的效果可能特别有用。