Global gene expression analyses of bystander and alpha particle irradiated normal human lung fibroblasts: synchronous and differential responses.
Global gene expression analyses of bystander and alpha particle irradiated normal human lung fibroblasts: synchronous and differential responses.
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旁观者和α粒子照射的正常人肺成纤维细胞的整体基因表达分析：同步和差异反应。
DOI：
10.1186/1755-8794-1-63
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发表时间：
2008-12-24
影响因子：
2.7
通讯作者：
Amundson SA
中科院分区：
文献类型：
--
作者：
Ghandhi SA;Yaghoubian B;Amundson SA
辐射旁观者效应是指未受辐射的细胞对受辐射细胞发出的信号作出反应，这种效应的存在现已得到充分证实。它引发了人们对低剂量电离辐射暴露所产生风险的解读的担忧。然而，旁观者反应所涉及的调控机制尚未得到很好的阐明。为了深入了解旁观者细胞中的信号通路，我们在原代人肺成纤维细胞受到旁观者效应和直接α粒子照射4小时后测量了全基因表达。
尽管像CDKN1A这样受p53调控的常见辐射反应基因在直接受照射的培养物中表达水平升高，但在旁观者细胞中它们几乎没有变化。相比之下，受NFκB调控的基因，如PTGS2（环氧合酶 - 2）、IL8和BCL2A1，在旁观者细胞和受照射细胞中的反应几乎相同。基因本体论和微阵列数据的通路分析证实了这一趋势，这表明旁观者细胞会产生完整的NFκB反应，但p53反应减弱或部分缺失。在时间进程分析中，对CDKN1A进行实时定量PCR测量显示，受照射细胞在预期的4小时出现表达峰值，而旁观者细胞则没有。相比之下，PTGS2、IL8和BCL2A1在旁观者细胞和直接受照射细胞中均出现两波表达，一波在照射后半小时达到峰值，另一波在照射后4 - 6小时达到峰值。
调节对电离辐射直接反应的两个主要转录枢纽也参与旁观者反应的调节，但程度差异很大。虽然旁观者细胞中p53反应途径的激活极小，但NFκB反应在受照射细胞和旁观者细胞中几乎相同。这种信号平衡的改变可能导致受照射细胞及其旁观者产生不同的结果，也许会使旁观者的存活率更高，并增加它们所遭受的任何长期损伤的风险。
The existence of a radiation bystander effect, in which non-irradiated cells respond to signals from irradiated cells, is now well established. It raises concerns for the interpretation of risks arising from exposure to low doses of ionizing radiation. However, the regulatory mechanisms involved in the bystander response have not been well elucidated. To provide insight into the signaling pathways responding in bystanders, we have measured global gene expression four hours after bystander and direct alpha particle exposure of primary human lung fibroblasts. Although common p53-regulated radiation response genes like CDKN1A were expressed at elevated levels in the directly exposed cultures, they showed little or no change in the bystanders. In contrast, genes regulated by NFκB, such as PTGS2 (cyclooxygenase-2), IL8 and BCL2A1, responded nearly identically in bystander and irradiated cells. This trend was substantiated by gene ontology and pathway analyses of the microarray data, which suggest that bystander cells mount a full NFκB response, but a muted or partial p53 response. In time-course analyses, quantitative real-time PCR measurements of CDKN1A showed the expected 4-hour peak of expression in irradiated but not bystander cells. In contrast, PTGS2, IL8 and BCL2A1 responded with two waves of expression in both bystander and directly irradiated cells, one peaking at half an hour and the other between four and six hours after irradiation. Two major transcriptional hubs that regulate the direct response to ionizing radiation are also implicated in regulation of the bystander response, but to dramatically different degrees. While activation of the p53 response pathway is minimal in bystander cells, the NFκB response is virtually identical in irradiated and bystander cells. This alteration in the balance of signaling is likely to lead to different outcomes in irradiated cells and their bystanders, perhaps leading to greater survival of bystanders and increased risk from any long-term damage they have sustained.
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DOI：
10.1016/j.mrfmmm.2005.08.012
发表时间：
2006-05-11
影响因子：
2.3
作者：
Belyakov, Oleg V.;Folkard, Melvyn;Michael, Barry D.
通讯作者：
Michael, Barry D.
影响因子：
3.4
作者：
Ding, LH;Shingyoji, M;Chen, DJ
通讯作者：
Chen, DJ
影响因子：
1.7
作者：
Chang, P. Y.;Bjornstad, K. A.;Blakely, E. A.
通讯作者：
Blakely, E. A.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.4
作者：
Cromheecke, M;Piers, BA;Hoekstra, HJ
通讯作者：
Hoekstra, HJ