Sherman M L, Datta R, Hallahan D E, Weichselbaum R R, Kufe D W
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston, MA.
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5663-6. doi: 10.1073/pnas.87.15.5663.
There is little known about the regulation of gene expression by ionizing radiation exposure. The present studies demonstrate transcriptional activation of a mammalian gene, the c-jun protooncogene, by x-rays. The c-jun gene encodes a component of the AP-1 protein complex and is important in early signaling events involved in various cellular functions. The increase in c-jun transcripts by ionizing radiation was time- and dose-dependent as determined by Northern blot analysis. Transcriptional run-on analysis demonstrated that ionizing radiation stimulates the rate of c-jun gene transcription. Furthermore, the half-life of c-jun RNA was prolonged in the absence of protein synthesis. These findings indicate that the increase in c-jun RNA observed after irradiation is regulated by transcriptional and posttranscriptional mechanisms. Moreover, the induction of c-jun by ionizing radiation was associated with an inverse dose rate effect in that decreasing the dose rate resulted in increased c-jun expression. The present results similarly demonstrate that ionizing radiation increases levels of c-fos transcripts as well as that of jun-B, another member of the jun family. Taken together, these results suggest a role for induction of early response genes in the pathophysiologic effects of ionizing radiation.
关于电离辐射暴露对基因表达的调控，目前所知甚少。本研究表明，X射线可使哺乳动物基因c-jun原癌基因发生转录激活。c-jun基因编码AP-1蛋白复合物的一个组分，在参与各种细胞功能的早期信号事件中起重要作用。通过Northern印迹分析确定，电离辐射使c-jun转录本增加呈时间和剂量依赖性。转录延伸分析表明，电离辐射刺激c-jun基因的转录速率。此外，在缺乏蛋白质合成的情况下，c-jun RNA的半衰期延长。这些发现表明，照射后观察到的c-jun RNA增加是由转录和转录后机制调控的。此外，电离辐射诱导c-jun与剂量率反比效应相关，即降低剂量率会导致c-jun表达增加。目前的结果同样表明，电离辐射会增加c-fos转录本以及jun家族的另一个成员jun-B的水平。综上所述，这些结果表明早期反应基因的诱导在电离辐射的病理生理效应中起作用。
