Jen Kuang-Yu, Cheung Vivian G
Departments of Pediatrics and Genetics, University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Genome Res. 2003 Sep;13(9):2092-100. doi: 10.1101/gr.1240103. Epub 2003 Aug 12.
The effects of ionizing radiation (IR) on the temporal transcriptional response of lymphoblastoid cells were investigated in this study. We used oligonucleotide microarrays to assess mRNA levels of genes in lymphoblastoid cells at various time points within 24 h following gamma-irradiation. We identified 319 and 816 IR-responsive genes following 3 Gy and 10 Gy of IR exposure, respectively, with 126 genes in common between the two doses. A high percentage of IR-responsive genes are involved in the control of cell cycle, cell death, DNA repair, DNA metabolism, and RNA processing. We determined the temporal expression profiles of the IR-responsive genes and assessed effects of IR dose on this temporal pattern of expression. By combining dose-response data with temporal profiles of expression, we have identified sets of coordinately responding genes. Through a genomic approach, we characterized a set of genes that are implicated in cellular adaptation to IR stress. These findings will allow a better understanding of complex processes such as radiation-induced carcinogenesis and the development of biomarkers for radiation exposure.
本研究调查了电离辐射（IR）对淋巴母细胞系细胞瞬时转录反应的影响。我们使用寡核苷酸微阵列评估γ射线照射后24小时内不同时间点淋巴母细胞系细胞中基因的mRNA水平。在分别接受3 Gy和10 Gy IR照射后，我们分别鉴定出319个和816个IR反应基因，两种剂量下共有126个基因相同。高比例的IR反应基因参与细胞周期调控、细胞死亡、DNA修复、DNA代谢和RNA加工。我们确定了IR反应基因的瞬时表达谱，并评估了IR剂量对这种瞬时表达模式的影响。通过将剂量反应数据与表达的时间谱相结合，我们鉴定出了协同反应基因集。通过基因组学方法，我们表征了一组与细胞对IR应激适应有关的基因。这些发现将有助于更好地理解诸如辐射诱导的致癌作用等复杂过程以及开发辐射暴露生物标志物。
