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The long-term effects of exposure to ionising radiation on gene expression in mice
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2020-10-11 , DOI: 10.1016/j.mrfmmm.2020.111723
Ayman Jafer , Nicolas Sylvius , Adeolu B. Adewoye , Yuri E. Dubrova

Despite great advancement in our understanding of the biological response to ionising radiation in mammals, a number of pertinent questions remain unanswered. For instance, the mechanisms underlying the long-term effects of acute radiation in vivo still eludes us. Here we report that acute exposure to X-rays in male mice significantly affects their transcriptome. Using microarrays and miRNA-sequencing, we profiled the gene expression pattern in the brain, the kidney, the liver and the sperm of irradiated and control from CBA/Ca and BALB/c in the timeline of 4 h, 24 h, 1 week and 10 weeks post-exposure. Acute exposure to 1 Gy of X-rays resulted in profound tissue- and strain-specific changes in gene expression pattern. There was profound change in the gene expression in the kidney of BALB/c irradiated mice over the period of 10 weeks after irradiation, whereas in the CBA/Ca strain the significant transcriptomic changes manifest over a shorter period of time up to 1 week post exposure. In the brain of irradiated CBA/Ca, significant changes in transcriptome were seen up to 10 weeks post-irradiation, while only short-term changes up to 4 h post-exposure was detected in the brain of irradiation BALB/c. Similarly, alteration in gene expression pattern was observed in the liver of irradiated BALB/c up to 10 weeks post-radiation, whereas only immediate but significant changes were observed in the CBA/Ca at 4 h post-irradiation. Furthermore, the analysis of miRNA in irradiated and control male mice also revealed highly tissue- and strain-specific changes in expression level, with no overlap between the differentially regulated miRNA genes across the three somatic tissues and the two inbred strains. We also analysed the pattern of miRNA expression in sperm of irradiated males, sacrificed at 24 h, 1 week and 10 weeks after irradiation. Only one miRNA (mmu-miR-217−5p) was significantly down-regulated in the CBA/Ca males. The results of our study may provide a plausible explanation for the delayed in vivo effects of irradiation.



中文翻译:

暴露于电离辐射对小鼠基因表达的长期影响

尽管我们对哺乳动物对电离辐射的生物学反应的理解有了很大的进步,但许多相关的问题仍未得到解答。例如,体内急性辐射长期影响的潜在机制仍然使我们望而却步。在这里,我们报告说,雄性小鼠急性暴露于X射线会显着影响其转录组。使用微阵列和miRNA测序,我们在4小时,24小时,1周和4小时的时间线中,分析了从CBA / Ca和BALB / c照射和控制的大脑,肾脏,肝脏和精子的基因表达模式。接触后10周。急性暴露于1 Gy的X射线会导致基因表达模式发生深刻的组织和菌株特异性变化。在辐照后10周内,BALB / c辐照小鼠肾脏中的基因表达发生了深刻变化,而在CBA / Ca株中,显着的转录组变化在暴露后直至1周内表现出更短的时间。在受辐照的CBA / Ca的大脑中,辐照后直至10周,转录组均发生了显着变化,而辐照后BALB / c的大脑仅检测到了长达4 h的短期变化。类似地,在辐射后直至10周,在受辐照的BALB / c的肝脏中观察到基因表达模式的改变,而在辐照后4 h,仅在CBA / Ca中观察到了立即但显着的变化。此外,对辐照和对照雄性小鼠中miRNA的分析还揭示了组织和菌株特异性表达水平的高度变化,在三个体细胞组织和两个自交系中差异调控的miRNA基因之间没有重叠。我们还分析了在照射后24 h,1周和10周处死的被辐照雄性精子中miRNA表达的模式。在CBA / Ca雄性中,只有一种miRNA(mmu-miR-217-5p)显着下调。我们的研究结果可能为延误提供合理的解释体内辐射的影响。

更新日期:2020-10-29
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