Gene expression following ionising radiation: Identification of biomarkers for dose estimation and prediction of individual response
Gene expression following ionising radiation: Identification of biomarkers for dose estimation and prediction of individual response
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DOI：
10.3109/09553002.2010.519424
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发表时间：
2011-02-01
影响因子：
2.6
通讯作者：
Badie, Christophe
中科院分区：
文献类型：
--
作者：
Kabacik, Sylwia;Mackay, Alan;Badie, Christophe
材料和方法：使用三种独立的技术进行了响应于辐射的基因表达的Euro积分分析。（微阵列，多重定量实时聚合酶链反应（MQRT-PCR）和nCounter（R）A（R）分析系统）在培养的人分裂淋巴细胞和来自相同供体的离体暴露的外周血白细胞中的应用。通过微阵列分析的暴露于电离辐射的转录应答中的Euro积分变化允许鉴定基因，所述基因可以使用MQRT PCR和另一种允许直接计数mRNA拷贝的技术精确测量。我们已经确定了在不同时间点暴露于2或4戈伊X射线后，血液和培养的淋巴细胞中所有个体的基因一致上调。下调的基因包括细胞周期蛋白、着丝粒和有丝分裂检查点基因，特别是那些与染色体不稳定性和癌症相关的基因仅在分裂的淋巴细胞中检测到。数据提供了证据，表明有许多基因似乎适合于使用外周血的生物剂量测定，包括sestrin 1（SESN 1）、生长停滞和DNA损伤诱导型45 α（GADD 45 A），细胞周期蛋白依赖性激酶抑制剂1A（CDKN 1A）、细胞周期蛋白G1（CCNG 1）、铁氧还蛋白还原酶（FDXR）、p53上调凋亡介导因子（BBC 3）和Mdm 2 p53结合蛋白同系物（MDM 2）。这些生物标志物可能用于大规模放射性事件后的分类，并用于监测放射治疗期间的辐射暴露。
Materials and methods: aEuro integral Analysis of gene expression in response to radiation was carried out using three independent techniques (Microarray, Multiplex Quantitative Real-Time Polymerase Chain Reaction (MQRT- PCR) and nCounter (R) A (R) Analysis System) in human dividing lymphocytes in culture and peripheral blood leukocytes exposed ex vivo from the same donors.Results: aEuro integral Variations in transcriptional response to exposure to ionising radiation analysed by microarray allowed the identification of genes which can be measured accurately using MQRT PCR and another technique allowing direct count of mRNA copies. We have identified genes which are consistently up-regulated following exposure to 2 or 4 Gy of X-rays at different time points, for all individuals in blood and cultured lymphocytes. Down-regulated genes including cyclins, centromeric and mitotic checkpoint genes, particularly those associated with chromosome instability and cancer could be detected in dividing lymphocytes only.Conclusions: aEuro integral The data provide evidence that there are a number of genes which seem suitable for biological dosimetry using peripheral blood, including sestrin 1 (SESN1), growth arrest and DNA damage inducible 45 alpha (GADD45A), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin G1 (CCNG1), ferredoxin reductase (FDXR), p53 up-regulated mediator of apoptosis (BBC3) and Mdm2 p53 binding protein homolog (MDM2). These biomarkers could potentially be used for triage after large-scale radiological incidents and for monitoring radiation exposure during radiotherapy.