目的 了解中等剂量和大剂量辐照对基因表达影响的差异性,以此探讨不同剂量γ射线生物学效应的分子基础。方法 正常人淋巴母细胞经2和10Gy^60Coγ射线照射后培养4h(未照射为对照组)。用包含有14022个基因的人类cDNA芯片分析基因转录谱,每个剂量点重复一次芯片检测,照射组与对照组细胞的差异表达基因表达量比值大于2或小于0.5,并且2次检测结果一致的基因点为有效差异表达基因。结果 2Gy照射后共有32个基因表达下凋,46个基因表达上调;10Gy照射后共有219个基因表达水平下降,26个基因表达水平上升,在两个剂量照射条件下都表达下调的基因至少有11个,同时上调的基因有9个,这些基因大多与细胞信号转导、细胞周期调控、DNA损伤修复、细胞凋亡等相关。结论 观察到中等剂量和大剂量辐照的相同诱导表达变化基因,10Gy剂量照射使大量的基因表达抑制,将导致细胞多方面的生理功能障碍。
Objective To compare the alterations of transcriptional profiles between 2 Gy and 10 Gy γ- ray irradiated cells. Methods Human normal lymphoblastoid cell AHH-1 line was irradiated with cobalt-60 γ rays of 2 Gy or 10 Gy. cDNA microarray, containing the probes corresponding to 14,022 human genes, was used to develop the transcriptional profiles of the cells at 4 h after irradiation. Double microarray was carried out for each dose group, and a 2-fold increase or decrease in signal intensity was treated as significant change in gene expression. Results The microarray assays showed 32 up-regulated genes and 46 down-regulated genes in cells irradiated with 2 Gy γ-rays, while there were 219 genes down-regulated and 26 genes up-regulated in cells irradiated with 10 Gy γ-rays. In addition, it was observed that llgenes were down-regulated and 9 genes up- regulated in both 2 Gy and 10 Gy irradiated groups, most of these altered genes could be related to signal transduction, cell cycle control, DNA repair and apoptosis. Conclusion Same genes were observed to be down- regulated or up-regulated with high or moderate dose irradiation. Ten grays irradiation can depress a great number of genes, which might lead to the failure of multiple cellular biological functions. This study shed light on molecular mechanisms of the diverse biological effects induced by different doses of ionizing radiation.