Molecular mechanisms of radiation-induced adaptive response in animal models

在历史上，低剂量辐射的生物效应是通过从高剂量辐射对日本原子弹幸存者、暴露的铀矿工团体、镭油漆工或核潜艇建造者的生物效应进行推断来估计的。这一推断假定，任何剂量，无论多么小，都是潜在的有害物质。然而，最近的研究表明，低剂量辐射的生物效应要复杂得多。生物具有很强的“抵抗”或“适应”辐射的能力。适应性反应是指在低剂量照射后获得的辐射抗性。在我的NSERC资助的项目中，我们已经表明，植物可以通过大幅重塑它们的基因组来适应切尔诺贝利地区的慢性辐射和生活。哺乳动物对低剂量辐射适应的分子机制是我的NSERC更新的重点。我们将与切尔诺贝利科学中心的研究人员合作，研究低剂量辐射暴露下实验室小鼠的分子和细胞变化。我们将解决以下问题：低剂量辐射诱导的细胞效应的分子本质是什么？哺乳动物细胞辐射暴露诱导的适应反应是否存在？触发它的机制是什么？表观遗传变化(DNA甲基化、组蛋白修饰、miRNAome改变)在辐射适应中扮演哪些角色？这个项目应该导致对基本的辐射适应过程、细胞生理学、基因毒性应激反应与分子进化。

Historically, the biological effects of low-dose radiation were estimated by extrapolating from the biological effects of high-dose radiation on Japanese atomic-bomb survivors, groups of exposed uranium miners, radium painters, or nuclear submarine builders. This extrapolation postulates that any dose no matter how small is potentially harmful. However, it was recently shown that the biological effects of low-dose radiation are considerably more complex. Living organisms have great capacity to 'withstand' or 'adapt' to radiation. Adaptive response is defined as the acquired radio-resistance after irradiation with low doses. In my NSERC funded project we have shown that plants can adapt to chronic irradiation and life in Chernobyl area by substantially re-shaping their genomes.  The phenomenon of radioadaptation of mammalian species has not been sufficiently explored. Molecular mechanisms of mammalian adaptation to low dose radiation are the focus of my NSERC renewal.In collaboration with the researchers of the Chernobyl Scientific Center we will address the molecular and cellular changes in the laboratory mice subjected to low dose radiation exposure.  The following questions will be addressed:What is the molecular nature of low dose radiation-induced effects in the cell?Does adaptive response induced by radiation exposure of mammalian cells exist and what are the mechanisms triggering it?Which roles do epigenetic changes (DNA methylation, histone modifications, miRNAome changes) play in radiation adaptation?This project should result in a solid understanding of basic radioadaptive processes, cellular physiology, genotoxic stress responses and molecular evolution.