Mechanisms underlying the effects of low doses of ionising radiation

目的：研究受照细胞的信号小体。 方法：细胞系和活的FISH将被用来研究受辐射的细胞和组织产生的信号的性质，并确定没有受到辐射但从受辐射的细胞接收信号的细胞和生物是如何处理这种信号的。我们团队最近的发现有力地表明，从受辐射的细胞和生物体传递到未受辐射的细胞和生物体的信号中存在一个物理成分。我们将用理论和实验的方法来检验低能光子参与的假设。 重要性和新颖性：自从人们接受非靶向效应(NTE)可以在未受辐射的细胞或受辐射细胞的远亲后代中测量以来，关于这些效应与放射生物学和辐射防护的相关性的讨论已经展开，因为它们增加了辐射反应的复杂性，并允许出现不像在“旧规则”下那样可预测的结果。重要的是要考虑与辐射防护和放射治疗等实际应用的相关性，但也令人感兴趣的是它们可能如何影响关于生物进化和适应的想法。我们小组的重要例子是：(I)数据表明细胞中旁观者机制是开或关的，并且“开”阈值似乎处于非常低的剂量(mGy值范围)；(Ii)数据表明适应性反应不仅在邻近细胞中被诱导，而且在接收旁观者信号的生物体中也被诱导；(Iii)数据表明长期暴露在阿尔法或伽马辐射下会在生物体中引起复杂的反应，这种反应可以是适应性的和保护性的。对这些信号机制的考虑可能也会对癌症生物学有所裨益，为癌细胞群体的调控以及这些群体如何与宿主相互作用提供了新的见解。这项提案试图澄清信号的性质，并确定这些影响如何导致组织各级的适应性变化。

Objective: To investigate the signalosome of irradiated cells. Approach: Cell lines and live fish which give a robust non-targeted radiation response will be used to investigate the nature of the signal produced by irradiated cells and tissues and to determine how this signal is processed by cells and organisms which are not irradiated but receive signals from irradiated cells. Recent discoveries by our group strongly suggest there is a physical component to the signal which passes from irradiated to non-irradiated cells and organisms. We will test the hypothesis that low energy photons are involved using theoretical and experimental approaches. Significance and Novelty: Ever since the acceptance that non-targeted effects (NTE) can be measured in unirradiated cells or distant progeny of irradiated cells, the discussion has developed about the relevance of these effects for radiobiology and radiation protection since they increase the complexity of the radiation response and allow for outcomes which are not as predictable as they were under the "old rules". It is important to consider relevance for practical applications such as radiation protection and radiotherapy but also of interest is how they might influence ideas about evolution and adaptation of organisms. Important examples from our group are (i) the data showing that bystander mechanisms are either on or off in cells and that the "on" threshold appears to be at a very low dose (mGy range), (ii) data suggesting that adaptive responses are induced not only in neighbouring cells but in organisms which receive bystander signals and (iii) data showing that chronic exposures to alpha or gamma irradiation lead to complex responses in organisms which can be adaptive and protective. It is likely that consideration of these signalling mechanisms could also be of benefit in cancer biology providing new insights into the regulation of cancer cell social groups and how these interact with the host. This proposal seeks to clarify the nature of the signal and to determine how these effects may lead to adaptive changes at various levels of organisation.