Delayed Effects of Exposure to a Moderate Radiation Dose on Transcription Profiles in Human Primary Fibroblasts
Delayed Effects of Exposure to a Moderate Radiation Dose on Transcription Profiles in Human Primary Fibroblasts
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DOI：
10.1002/em.20591
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发表时间：
2011-03-01
影响因子：
2.8
通讯作者：
Sakamoto-Hojo, Elza T.
中科院分区：
文献类型：
--
作者：
Mello, Stephano S.;Fachin, Ana L.;Sakamoto-Hojo, Elza T.
电离辐射 (IR) 广泛用于医疗和非医疗应用，对人类健康构成潜在威胁。了解受辐射细胞基因表达变化可能有助于建立有效的辐射防护范例。红外线诱导的 DNA 损伤会触发一系列复杂的信号转导。最近，全基因组方法已经能够检测各种辐射剂量下基因表达的变化。然而，轻度剂量的红外线的延迟或长期生物效应仍然很大程度上未知。本研究的主要目的是研究中等剂量的伽马射线 (50 cGy) 对辐照后 6 天基因表达的影响。使用 cDNA 微阵列的基因表达显示 59 个基因的表达发生了统计学上的显着变化 (FDR < 0.07)，这些基因的功能与细胞周期控制、蛋白质运输、泛素循环、Rho-GTPA 酶途径、蛋白磷酸酶信号传导、氧化还原酶控制和应激反应有关。还通过不太严格的方法选择了一组 464 个基因，我们证明这组更广泛的基因可以有效地区分受辐射样品与未受辐射样品，从而定义人类原代成纤维细胞中的长期 IR 特征。我们的研究结果支持通过基因表达谱的变化可检测到对温和剂量的红外线存在持续反应。这些结果提供了对在人类原代细胞中观察到的延迟效应以及长期反应在肿瘤转化中的作用的深入了解。环境。摩尔。诱变剂。 52: 117-129, 2011。(C) 2010Wiley-Liss, Inc.
Ionizing radiation (IR) is used in a wide variety of medical and nonmedical applications and poses a potential threat to human health. Knowledge of changes in gene expression in irradiated cells may be helpful for the establishment of effective paradigms for radiation protection. IR-induced DNA damage triggers a complex cascade of signal transduction. Recently, genome-wide approaches have allowed the detection of alterations in gene expression across a wide range of radiation doses. However, the delayed or long-term biological effects of mild-doses of IR remain largely unknown. The main objective of the present study was to investigate the effects of a moderate dose of gamma-rays (50 cGy) on gene expression 6 days post-irradiation. Gene expression using cDNA microarrays revealed statistically significant changes in the expression of 59 genes (FDR < 0.07), whose functions are related to cell-cycle control, protein trafficking, ubiquitin cycle, Rho-GTPAse pathway, protein phosphatase signalization, oxidoreductase control, and stress response. A set of 464 genes was also selected by a less stringent approach, and we demonstrate that this broader set of genes can efficiently distinguish the irradiated samples from the unirradiated, defining a long-term IR signature in human primary fibroblasts. Our findings support the existence of persistent responses to mild doses of IR detectable by changes in gene expression profiles. These results provide insight into delayed effects observed in human primary cells as well as the role of long-term response in neoplastic transformation. Environ. Mol. Mutagen. 52: 117-129, 2011. (C) 2010Wiley-Liss, Inc.