Physical transmission of bystander signals following ionising radiation exposure

辐射是一个让人讨厌的词，主要是因为它是一种已知的致癌物质。因此，它受到严格的管制，除非用于医学。关于低剂量照射的真实的风险以及可能决定这些风险的相关机制，存在着相当大的争议。目前有一个线性剂量反应关系的假设，但这似乎是一个妥协，以满足对立的派别，而不是任何基于良好的科学。随着越来越依赖核能作为碳中性能源的可能性，以及在CT扫描等医疗诊断测试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驱动剂量反应的因素。我们的团队多年来一直专注于这个问题，并描述了非靶向效应（NTE），如旁观者效应和基因组不稳定性。 这些是细胞、器官或生物体中的效应，这些效应没有被辐射轨迹穿过，而是从那些穿过的细胞、器官或生物体接收信号。我们以前的研究表明，这些NTE占主导地位的辐射剂量反应后，低剂量暴露，这表明在低剂量区的机制是非常不同的，众所周知的双链DNA断裂后发生的高剂量。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小于高剂量暴露的预期风险。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信号。UVA光子已被检测到来自受照射的细胞，这些光子已被证明会引发细胞和生物体中的一系列反应，这些反应与“好”和“坏”结果都相关。 目前的建议旨在了解的物理过程中涉及的初始电离辐射能量的转换，导致紫外线发射，以及如何捕获紫外线启动和消除的特征旁观者效应。 这些实验将建立在以前的工作基础上，并试图确定生物材料发射的光谱以及发射光子的后续命运，目的是了解所涉及的生物物理过程。只有了解基本的物理机制，才有可能更好地确定生物下游后果，并提出保护战略。

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 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.