Development of gene expression signatures for practical radiation biodosimetry. Homo sapiens

To further development of our gene expression approach to biodosimetry, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish radiation dose across an exposure range relevant for medical decision-making in a radiological emergency. Human peripheral blood from healthy donors was irradiated ex vivo, and a 74-gene consensus signature was identified that distinguished between four radiation doses (0.5, 2, 5 and 8 Gy) and control samples. The same set of genes separated samples by exposure level at both six and 24 hours after treatment, with overlap evident only at the highest two doses (5 and 8 Gy). Expression of five genes (CDKN1A, FDXR, SESN1, BBC3 and PHPT1) from this signature was quantified in the same RNA samples by real-time PCR, confirming low variability between donors as well as the predicted radiation response pattern. Keywords: Dose Response, stress response, radiation response, biodosimetry Overall design: Radiation induced gene expression in human blood was measured at 6 and 24 hours after exposure to doses of 0, 0.5, 2, 5 and 8 Gy g-rays. Five independent experiments were performed at each time (6 or 24 hours) using different donors for each experiment

为推进我们用于生物剂量学的基因表达研究方法的发展，我们采用全基因组微阵列表达谱作为发现平台，旨在筛选出可在放射应急医疗决策相关的照射剂量范围内区分辐射剂量的潜在基因。我们对健康供者的外周血开展离体辐照实验，最终鉴定出包含74个基因的共识特征标签，该标签可有效区分4种辐射剂量（0.5、2、5和8 Gy）及对照样本。该基因集在辐照后6小时与24小时两个时间点均可依据暴露水平对样本进行区分，且仅在最高的两个剂量组（5和8 Gy）中存在明显的表达重叠。我们通过实时定量PCR对该特征标签中的5个基因（CDKN1A、FDXR、SESN1、BBC3及PHPT1）在同一份RNA样本中的表达量进行了定量检测，验证了供者间较低的表达变异度以及预期的辐射应答模式。关键词：剂量应答、应激应答、辐射应答、生物剂量学。整体实验设计：在暴露于0、0.5、2、5及8 Gy γ射线后，分别于6小时与24小时两个时间点检测人血液中的辐射诱导基因表达。本研究在每个时间点（6小时或24小时）均开展了5次独立实验，每次实验均使用不同的健康供者样本。