Jin Young-Woo, Na Young-Ji, Lee Young-Ju, An Sungkwan, Lee Jung Eun, Jung Meeseon, Kim Heesun, Nam Seon Young, Kim Cha Soon, Yang Kwang Hee, Kim Seung Up, Kim Woo Kyung, Park Woong-Yang, Yoo Keun-Young, Kim Chong Soon, Kim Ju Han
Division of Radiation Effect Research, Radiation Health Research Institute of KHNP, Seoul 132-703, Korea.
Oncol Rep. 2008 Jan;19(1):135-44.
We focused on the transcriptional responses induced by low and very low doses of ionizing radiation with time effect. Regardless of their importance only a few limited studies have been done. Here we applied a large-scale gene transcript profile to elucidate the genes and biological pathways. Immortalized human mesenchymal stem cells were irradiated with 0.01, 0.05, 0.2 and 1 Gy of gamma radiation and total RNA was extracted from each cell line at 1, 4, 12 and 48 h after exposure. The essential transcriptional responses were identified according to dose and time. A total of 6,016 genes showed altered expression patterns at more than one time point or dose level among the investigated 10,800 genes. Genes that showed dose-dependent expression responses were involved in signal transduction, regulation of transcription, proteolysis, peptidolysis and metabolism. Those that showed time-dependent responses were divided into two distinct groups: the up-and-down group was associated with 'cellular defense mechanisms' such as apoptosis, cell adhesion, stress response and immune response and the down-and-up group with 'fundamental cellular processes' such as DNA replication, mitosis, RNA splicing, DNA repair and translation initiation. Genes showing both dose-and time-dependent responses exhibited a mixture of both features. A highly non-linear relationship between the IR dose and the transcriptional relative response was obtained from the dose-dependent group. The time-dependent group also exhibited a non-linear relationship as the complex effect group did. Some of the early-reactive-phase (1-4 h) genes showed a differential expression response to 0.01, 0.05 and 0.2 Gy but were unresponsive to 1 Gy. Some of the late-recovery-phase (12-48 h) genes showed a differential expression to 1 Gy but were relatively unresponsive to other doses. We further characterized the gene expression patterns that could be implicated in the molecular mechanism of the cellular responses to low and very low-dose irradiation.
我们重点研究了低剂量和极低剂量电离辐射随时间效应所诱导的转录反应。尽管其重要性不言而喻，但相关的有限研究却为数不多。在此，我们运用大规模基因转录谱来阐明相关基因及生物学途径。将永生化人骨髓间充质干细胞分别用0.01、0.05、0.2和1 Gy的γ射线进行照射，并在照射后1、4、12和48小时从每个细胞系中提取总RNA。根据剂量和时间确定了基本的转录反应。在所研究的10,800个基因中，共有6,016个基因在多个时间点或剂量水平呈现出表达模式的改变。显示剂量依赖性表达反应的基因涉及信号转导、转录调控、蛋白水解、肽水解和代谢。显示时间依赖性反应的基因分为两个不同的组：上下波动组与“细胞防御机制”相关，如细胞凋亡、细胞黏附、应激反应和免疫反应；而下上波动组与“基本细胞过程”相关，如DNA复制、有丝分裂、RNA剪接、DNA修复和翻译起始。显示剂量和时间依赖性反应的基因则兼具这两种特征。从剂量依赖性组中获得了IR剂量与转录相对反应之间高度非线性的关系。时间依赖性组与复合效应组一样也呈现出非线性关系。一些早期反应阶段（1 - 4小时）的基因对0.01、0.05和0.2 Gy呈现出差异表达反应，但对1 Gy无反应。一些晚期恢复阶段（12 - 48小时）的基因对1 Gy呈现出差异表达，但对其他剂量相对无反应。我们进一步对可能与细胞对低剂量和极低剂量辐射反应的分子机制相关的基因表达模式进行了表征。
