Physical transmission of bystander signals following ionising radiation exposure

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，除非在医学上使用，否则它的管理非常严格。关于低剂量照射的实际风险和确定这些风险的相关机制存在相当大的争议。目前有一种线性剂量反应关系的假设，但这似乎更多地是为了满足反对派别的妥协，而不是基于良好的科学。随着越来越多地依赖核能作为碳中性能源，以及在医学诊断试验（如CT扫描）中越来越多地使用辐射，迫切需要更好地了解低剂量照射后导致剂量反应的因素。我们的团队多年来一直关注这个问题，并描述了非靶向效应（NTE），如旁观者效应和基因组不稳定性。这是一种对细胞、器官或有机体的影响，这些细胞、器官或有机体没有被辐射轨迹穿过，但却从辐射轨迹穿过的细胞接收到信号。我们之前的研究表明，这些NTE在低剂量暴露后的辐射剂量反应中占主导地位，这表明在低剂量区域的作用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，有必要了解低剂量照射后发生的情况，以及低剂量照射的风险是否大于或小于高剂量照射的预期风险。在上一次NSERC发现资助期间，我们的实验室发现难以捉摸的主要旁观者信号是物理的，而不是最初认为的化学的。已经检测到来自辐照细胞的UVA光子，这些光子已被证明会在细胞和生物体中引发一系列与“好”和“坏”结果相关的反应。目前的建议旨在了解在初始电离辐射能量的转导中所涉及的物理过程，以引起紫外线发射，以及如何捕获紫外线以启动和转导特征的旁观者效应。实验将建立在以前的工作基础上，并试图描述生物材料发射的光谱和随后发射的光子，目的是理解所涉及的生物物理过程。只有了解了基本的物理机制，才有可能更好地确定生物下游后果并提出保护策略。

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 thespectrum of emissions from the biological material and the subsequentfate of emitted photons with the aim of understanding the biophysicalprocesses involved. Only when the basic physical mechanisms are understood will it be possible to better define the biological downstream consequences and propose protective strategies.