Pawlik Alexandre, Delmar Paul, Bosse Sebastien, Sainz Laurie, Petat Cyrille, Pietu Genevieve, Thierry Dominique, Tronik-Le Roux Diana
Commissariat a l'Energie Atomique (CEA), Evry, France.
Int J Radiat Biol. 2009 Aug;85(8):656-71. doi: 10.1080/09553000903020024.
To identify transcriptional gene-networks involved in the early in vivo response of liver cells to radiation exposure and improve our understanding of the molecular processes responsible for tissue radiosensitivity.
Transcriptome variations of liver RNA samples were measured 3 hours post-irradiation using microarray technology. The results were confirmed and extended using real-time polymerase-chain-reaction (RT-PCR).
We identified quantitative changes in the expression of 126 genes, most of which were observed for the first time. We show that some modifications, such as the upregulation of the cyclin-dependent kinase inhibitor 1A (Cdkn1A) gene, persisted for at least two months after the initial exposure. Other genes regulated by the transformation-related protein 53 (Trp53/p53) such as Bcl2-associated X protein (Bax) or etoposide-induced-2.4 (Ei24/PIG8) were not upregulated. Grouping differentially expressed genes into functional categories revealed that the primary response of liver cells to radiation exposure was the enhancement of oxidoreductase activity and inhibition of cell proliferation, involving cell cycle progression and apoptosis-related genes.
The data provides evidence of gene expression modifications associated with the hepatic response to radiation exposure. One of the main differences observed with radiation-sensitive tissues such as the spleen was cell proliferation. The comparison of our data with transcriptome modifications in different biological models enabled the identification of networks of genes that might be co-regulated. Overall, our expression data revealed genes and cellular pathways that might help to improve our understanding of the molecular basis underlying tissue radiosensitivity and to identify possible targets for novel therapeutic strategies.
确定参与肝细胞对辐射暴露早期体内反应的转录基因网络，并增进我们对负责组织放射敏感性的分子过程的理解。
使用微阵列技术在照射后3小时测量肝脏RNA样本的转录组变化。结果通过实时聚合酶链反应（RT-PCR）得到证实和扩展。
我们鉴定出126个基因表达的定量变化，其中大多数是首次观察到的。我们发现一些变化，如细胞周期蛋白依赖性激酶抑制剂1A（Cdkn1A）基因的上调，在初次暴露后至少持续两个月。其他受转化相关蛋白53（Trp53/p53）调控的基因，如Bcl2相关X蛋白（Bax）或依托泊苷诱导-2.4（Ei24/PIG8）并未上调。将差异表达基因分组到功能类别中显示，肝细胞对辐射暴露的主要反应是氧化还原酶活性增强和细胞增殖抑制，涉及细胞周期进程和凋亡相关基因。
数据提供了与肝脏对辐射暴露反应相关的基因表达修饰的证据。在诸如脾脏等放射敏感组织中观察到的主要差异之一是细胞增殖。将我们的数据与不同生物学模型中的转录组修饰进行比较，能够鉴定可能共同调控的基因网络。总体而言，我们的表达数据揭示了可能有助于增进我们对组织放射敏感性分子基础的理解并确定新型治疗策略可能靶点的基因和细胞途径。
