Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation.
Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation.
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DOI：
10.4103/0971-6203.152249
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发表时间：
2015-01
影响因子：
0.9
通讯作者：
Fardid R
中科院分区：
文献类型：
--
作者：
Azimian H;Bahreyni-Toossi MT;Rezaei AR;Rafatpanah H;Hamzehloei T;Fardid R
淋巴细胞对电离辐射诱导的应激表现出复杂的分子反应。许多这些反应是通过基因表达的修饰介导的，包括参与细胞凋亡的基因。本研究的主要目的是评估低剂量电离辐射对凋亡基因表达水平的影响。第二个目标是估计低剂量电离辐射对基因表达的时间效应。通过来自钴-60源的γ射线将培养物中的单核细胞暴露于范围为20至100 mGy的各种剂量值。在暴露后4、24、48、72和168小时取样用于基因表达分析。在不同的时间间隔，通过相对定量实时聚合酶链反应（PCR）检测两个凋亡基因：BAX（促凋亡）和Bcl-2（抗凋亡）的表达水平。外周血单核细胞（PBMC）的放射敏感性通过Bcl-2/BAX比值（作为放射敏感性的预测标志物）进行测量。进行非参数双独立样本Mann-Whitney U检验以比较基因表达的平均值。这项研究的结果表明，低剂量的γ辐射可以诱导新鲜分离的人PBMC的BAX基因的早期下调;然而，这些变化在168小时后恢复到接近正常水平。在大多数情况下，Bcl-2抗凋亡基因的表达上调。暴露于低剂量γ辐射后4小时，凋亡基因表达被改变，这表现为适应性反应。这些基因表达的修饰似乎是早期辐射抗性反应的主要途径。在我们的研究中，我们发现这些变化是暂时的，并在一周内完全消失。
Lymphocytes have demonstrated complex molecular responses to induced stress by ionizing radiation. Many of these reactions are mediated through modifications in gene expressions, including the genes involved in apoptosis. The primary aim of this study was to assess the effects of low doses of ionizing radiation on the apoptotic genes, expression levels. The secondary goal was to estimate the time-effect on the modified gene expression caused by low doses of ionizing radiation. Mononuclear cells in culture were exposed to various dose values ranged from 20 to 100 mGy by gamma rays from a Cobalt-60 source. Samples were taken for gene expression analysis at hours 4, 24, 48, 72, and 168 following to exposure. Expression level of two apoptotic genes; BAX (pro-apoptotic) and Bcl-2 (anti-apoptotic) were examined by relative quantitative real-time polymerase chain reaction (PCR), at different time intervals. Radio-sensitivity of peripheral blood mononucleated cells (PBMCs) was measured by the Bcl-2/BAX ratio (as a predictive marker for radio-sensitivity). The non-parametric two independent samples Mann–Whitney U-test were performed to compare means of gene expression. The results of this study revealed that low doses of gamma radiation can induce early down-regulation of the BAX gene of freshly isolated human PBMCs; however, these changes were restored to near normal levels after 168 hours. In most cases, expression of the Bcl-2 anti-apoptotic gene was up-regulated. Four hours following to exposure to low doses of gamma radiation, apoptotic gene expression is modified, this is manifested as adaptive response. Modification of these gene expressions seems to be a principle pathway in the early radioresistance response. In our study, we found that these changes were temporary and faded completely within a week.