首页> 外文期刊>International Journal of Radiation Biology: Covering the Physical, Chemical, Biological, and Medical Effects of Ionizing and Non-ionizing Radiations >Differential gene expression in human fibroblasts after alpha-particle emitter 211At compared with 60Co irradiation
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Differential gene expression in human fibroblasts after alpha-particle emitter 211At compared with 60Co irradiation

机译:α粒子发射体211At与60Co照射后人类成纤维细胞中的差异基因表达

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Purpose: The aim of this study was to identify gene expression profiles distinguishing alpha-particle 211At and 60Co irradiation. Materials and methods: Gene expression microarray profiling was performed using total RNA from confluent human fibroblasts 5 hours after exposure to 211At labeled trastuzumab monoclonal antibody (0.25, 0.5, and 1 Gy) and 60Co (1, 2, and 3 Gy). Results: We report gene expression profiles that distinguish the effect different radiation qualities and absorbed doses have on cellular functions in human fibroblasts. In addition, we identified commonly expressed transcripts between 211At and 60Co irradiation. A greater number of transcripts were modulated by 211At than 60Co irradiation. In addition, down-regulation was more prevalent than up-regulation following 211At irradiation. Several biological processes were enriched for both irradiation qualities such as transcription, cell cycle regulation, and cell cycle arrest, whereas mitosis, spindle assembly checkpoint, and apoptotic chromosome condensation were uniquely enriched for alpha particle irradiation. Conclusions: LET-dependent transcriptional modulations were observed in human fibroblasts 5 hours after irradiation exposure. These findings suggest that in comparison with 60Co, 211At has the clearest influence on both tumor protein p53-activated and repressed genes, which impose a greater overall burden to the cell following alpha particle irradiation.
机译:目的:本研究的目的是鉴定区分α粒子211At和60Co照射的基因表达谱。材料和方法:基因表达微阵列分析是在接触211At标记的曲妥珠单抗单克隆抗体(0.25、0.5和1 Gy)和60Co(1、2和3 Gy)5小时后,使用来自汇合人成纤维细胞的总RNA进行的。结果:我们报告基因表达谱,以区分不同的辐射质量和吸收剂量对人成纤维细胞功能的影响。另外,我们鉴定了在211At和60Co照射之间通常表达的转录本。 211At比60Co辐射能调节更多的转录本。另外,在211At照射后,下调比上调更普遍。几种生物学过程的辐照质量(例如转录,细胞周期调控和细胞周期停滞)都得到了丰富,而有丝分裂,纺锤体装配检查点和凋亡染色体凝结则被独特地富含了α粒子辐照。结论:照射后5小时,在人成纤维细胞中观察到了LET依赖的转录调节。这些发现表明,与60Co相比,211At对肿瘤蛋白p53激活和阻抑的基因影响最明显,这在α粒子辐照后对细胞造成了更大的总体负担。

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