Physical transmission of bystander signals following ionising radiation exposure

电离辐射暴露后旁观者信号的物理传输

• 批准号: RGPIN-2017-06223
• 负责人: Mothersill, Carmel
• 金额: $ 2.62万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=660340
• 关键词: Physical; transmission; bystander; signals; following

Radiation is a word that frightens people mainly because it is a known cancer-causing agent. Therefore it is regulated very strictly unless being used in medicine. There is considerable controversy concerning the real risks of low dose exposures and the relevant mechanisms which could determine those risks. Currently there is an assumption of a linear dose response relationship but that appears to be more a compromise to satisfy opposing factions rather than anything based on good science. With the possibility of increased dependence on nuclear power as a carbon neutral energy source, and increased use of radiation in medical diagnostic tests such as CT scans, there is an urgent need to gain a better understanding of the factors driving the dose response after low dose exposure. Our group have focused on this question for many years and have characterised non-targeted effects (NTE) such as the bystander effect and genomic instability. These are effects in cells, organs or organisms which did not get traversed by the radiation track but received signals from those that did. Our previous studies have shown that these NTE dominate the radiation dose response after low dose exposure, suggesting that the mechanisms operating in the low dose region are very different to the well known double strand DNA breaks which occur after high doses. This makes it imperative to understand what is going on after low dose exposure and whether the risk of low doses is greater or less than would be expected from high dose exposure. During the last NSERC Discovery grant period our laboratory discovered that the elusive primary bystander signal is physical not chemical as initially thought. UVA photons have been detected coming from irradiated cells and these have been shown to trigger a range of responses in cells and organisms which are associated both with “good” and “bad” outcomes. The current proposal seeks to understand the physical processes involved in the transduction of the initial ionising radiation energy to cause UV emission and how the UV is captured to initiate and transduce the characteristic bystander effects. The experiments will build on previous work and seek to characterise the*spectrum of emissions from the biological material and the subsequent*fate of emitted photons with the aim of understanding the biophysical*processes involved. Only when the basic physical mechanisms are understood will it be possible to better define the biological downstream consequences and propose protective strategies.

辐射这个词之所以让人害怕，主要是因为它是一种已知的致癌物质。因此，除非用于医药，否则它的监管非常严格。关于低剂量暴露的真正风险以及可以确定这些风险的相关机制，存在着相当大的争议。目前有一种假设是线性剂量反应关系，但这似乎更多地是为了满足对立派别的妥协，而不是任何基于良好科学的东西。随着对核电作为碳中性能源的依赖增加，以及在CT扫描等医学诊断测试中越来越多地使用辐射，迫切需要更好地了解驱动低剂量暴露后剂量反应的因素。我们小组多年来一直关注这一问题，并以非靶向效应(NTE)为特征，如旁观者效应和基因组不稳定。这些是对细胞、器官或生物体的影响，它们没有被辐射轨迹穿过，但收到了来自辐射轨迹的信号。我们以前的研究表明，这些NTE主导着低剂量照射后的辐射剂量反应，这表明在低剂量区工作的机制与众所周知的高剂量后发生的双链DNA断裂非常不同。因此，必须了解低剂量暴露后发生了什么，以及低剂量暴露的风险是否大于或低于高剂量暴露的预期风险。在上一次NSERC发现拨款期间，我们的实验室发现，难以捉摸的主要旁观者信号是物理信号，而不是最初认为的化学信号。已检测到来自受辐射细胞的UVA光子，这些光子已被证明在细胞和生物体中触发一系列反应，与“好的”和“坏的”结果都有关。目前的提案试图了解在转换初始电离辐射能量以导致紫外线发射的过程中涉及的物理过程，以及如何捕获紫外线以启动和传递特征的旁观者效应。这些实验将建立在以前工作的基础上，并试图表征生物材料发射的光谱以及随后发射的光子的命运，目的是了解涉及的生物物理过程。只有了解了基本的物理机制，才有可能更好地界定生物下游后果并提出保护策略。