Kis Enikö, Szatmári Tünde, Keszei Márton, Farkas Róbert, Esik Olga, Lumniczky Katalin, Falus András, Sáfrány Géza
Department of Molecular and Tumor Radiobiology, NCPH-Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary.
Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1506-14. doi: 10.1016/j.ijrobp.2006.08.004. Epub 2006 Oct 25.
To identify radiation-induced early transcriptional responses in primary human fibroblasts and understand cellular pathways leading to damage correction.
Primary human fibroblast cell lines were irradiated with 2 Gy gamma-radiation and RNA isolated 2 h later. Radiation-induced transcriptional alterations were investigated with microarrays covering the entire human genome. Time- and dose dependent radiation responses were studied by quantitative real-time polymerase chain reaction (RT-PCR).
About 200 genes responded to ionizing radiation on the transcriptional level in primary human fibroblasts. The expression profile depended on individual genetic backgrounds. Thirty genes (28 up- and 2 down-regulated) responded to radiation in identical manner in all investigated cells. Twenty of these consensus radiation response genes were functionally categorized: most of them belong to the DNA damage response (GADD45A, BTG2, PCNA, IER5), regulation of cell cycle and cell proliferation (CDKN1A, PPM1D, SERTAD1, PLK2, PLK3, CYR61), programmed cell death (BBC3, TP53INP1) and signaling (SH2D2A, SLIC1, GDF15, THSD1) pathways. Four genes (SEL10, FDXR, CYP26B1, OR11A1) were annotated to other functional groups. Many of the consensus radiation response genes are regulated by, or regulate p53. Time- and dose-dependent expression profiles of selected consensus genes (CDKN1A, GADD45A, IER5, PLK3, CYR61) were investigated by quantitative RT-PCR. Transcriptional alterations depended on the applied dose, and on the time after irradiation.
The data presented here could help in the better understanding of early radiation responses and the development of biomarkers to identify radiation susceptible individuals.
鉴定原发性人成纤维细胞中辐射诱导的早期转录反应，并了解导致损伤修复的细胞途径。
用2 Gy的γ射线照射原发性人成纤维细胞系，2小时后分离RNA。用覆盖整个人类基因组的微阵列研究辐射诱导的转录改变。通过定量实时聚合酶链反应（RT-PCR）研究时间和剂量依赖性辐射反应。
约200个基因在原发性人成纤维细胞的转录水平上对电离辐射有反应。表达谱取决于个体遗传背景。在所有研究的细胞中，有30个基因（28个上调和2个下调）以相同方式对辐射有反应。这些共有辐射反应基因中的20个在功能上进行了分类：其中大多数属于DNA损伤反应（GADD45A、BTG2、PCNA、IER5）、细胞周期和细胞增殖调节（CDKN1A、PPM1D、SERTAD1、PLK2、PLK3、CYR61）、程序性细胞死亡（BBC3、TP53INP1）和信号传导（SH2D2A、SLIC1、GDF15、THSD1）途径。四个基因（SEL10、FDXR、CYP26B1、OR11A1）被注释到其他功能组。许多共有辐射反应基因受p53调节或调节p53。通过定量RT-PCR研究了选定共有基因（CDKN1A、GADD45A、IER5、PLK3、CYR61）的时间和剂量依赖性表达谱。转录改变取决于所施加的剂量以及照射后的时间。
本文提供的数据有助于更好地理解早期辐射反应，并有助于开发用于识别辐射易感个体的生物标志物。
