Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Mutat Res. 2011 Jun 17;722(2):119-30. doi: 10.1016/j.mrgentox.2011.03.002. Epub 2011 Apr 15.
We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose-response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of ∼80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10cGy, some with suggestive evidence that transcription was modulated at doses below 1cGy. MYC, FOS and TP53 were the major network nodes of the low-dose-response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.
我们研究了人细胞对低剂量辐射的转录反应的低剂量依赖性，以表征与剂量反应曲线相关的形状和生物学功能，并确定低剂量表达基因在细胞和组织中的常见和保守功能。我们通过转录组谱分析、qPCR 和生物信息学，比较假照射样本，分析了来自两个无关个体的人类淋巴母细胞 (HL) 细胞在 1-10cGy 范围内的梯度剂量辐射暴露。一组约 80 个基因在两条细胞系中表现出一致的反应；这些基因与稳态机制（例如膜信号转导、分子转运）、亚细胞位置（例如高尔基体和内质网）以及涉及多种信号转导途径有关。大多数辐射调节基因在 1-10cGy 之间呈平台样反应，有些证据表明在 1cGy 以下的剂量下转录被调节。在 HL 细胞中，MYC、FOS 和 TP53 是低剂量反应的主要网络节点。将我们在 HL 细胞中的低剂量表达发现与先前在全身暴露后小鼠大脑、人角质形成细胞培养物和内皮细胞培养物中的研究进行比较，表明低剂量辐射反应的某些成分在细胞类型和组织中广泛保守，与增殖状态无关。
