Low-dose irradiation alters the transcript profiles of human lymphoblastoid cells including genes associated with cytogenetic radioadaptive response
Low-dose irradiation alters the transcript profiles of human lymphoblastoid cells including genes associated with cytogenetic radioadaptive response
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DOI：
10.1667/rr3356.1
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Wyrobek, AJ
中科院分区：
文献类型：
--
作者：
Coleman, MA;Yin, E;Wyrobek, AJ
低剂量电离辐射改变了哺乳动物细胞的基因表达谱，但人们对这些变化的基本细胞机制或其对基因组稳定性的影响知之甚少。我们研究了暴露于5cGy的人淋巴母细胞系的细胞遗传学适应性反应（预激剂量），随后为2戈伊（激发剂量）与接受单一2-戈伊剂量的细胞进行比较，以（a）确定引发剂量如何影响可再现适应和非适应细胞系中随后的基因转录物表达，和（B）鉴定与攻击剂量后染色体损伤程度降低相关的基因转录物。使用寡核苷酸阵列和攻击剂量后4小时获得的RNA评价转录谱。具有受5-cGy引发剂量影响的转录物的一组145个基因（错误发现率= 5%）分为两类：（a）一组共同基因，其类似地受5-cGy引发剂量调节，而不管细胞随后是否适应，以及（B）根据显示适应性或非适应性结果的细胞系具有差异转录的基因。常见的引发剂量反应基因显示蛋白质合成基因上调，代谢和信号转导基因下调（> 10倍差异）。与随后的适应性和非适应性结果相关的基因涉及DNA修复、应激反应、细胞周期控制和凋亡。我们的研究结果支持TP 53相关功能在控制低剂量细胞遗传学辐射适应性反应中的重要性，并表明某些低剂量诱导的细胞功能改变可预测随后基因组损伤的风险。(c)2005年，辐射研究协会。
Low-dose ionizing radiation alters the gene expression profiles of mammalian cells, yet there is little understanding of the underlying cellular mechanisms responsible for these changes or of their consequences for genomic stability. We investigated the cytogenetic adaptive response of human lymphoblastoid cell lines exposed to 5 cGy (priming dose) followed by 2 Gy (challenge dose) compared to cells that received a single 2-Gy dose to (a) determine how the priming dose influences subsequent gene transcript expression in reproducibly adapting and non-adapting cell lines, and (b) identify gene transcripts that are associated with reductions in the magnitude of chromosomal damage after the challenge dose. The transcript profiles were evaluated using oligonucleotide arrays and RNA obtained 4 h after the challenge dose. A set of 145 genes (false discovery rate = 5%) with transcripts that were affected by the 5-cGy priming dose fell into two categories: (a) a set of common genes that were similarly modulated by the 5-cGy priming dose irrespective of whether the cells subsequently adapted or not and (b) genes with differential transcription in accordance with the cell lines that showed either adaptive or non-adaptive outcomes. The common priming-dose response genes showed up-regulation for protein synthesis genes and down-regulation of metabolic and signal transduction genes (> 10-fold differences). The genes associated with subsequent adaptive and non-adaptive outcomes involved DNA repair, stress response, cell cycle control and apoptosis. Our findings support the importance of TP53-related functions in the control of the low-dose cytogenetic radioadaptive response and suggest that certain low-dose-induced alterations in cellular functions are predictive for the risk of subsequent genomic damage. (c) 2005 by Radiation Research Society.