Mechanisms underlying the effects of low doses of ionising radiation

低剂量电离辐射影响的机制

• 批准号: 293153-2012
• 负责人: Mothersill, Carmel
• 金额: $ 3.72万
• 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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571405
• 关键词: Mechanisms; underlying; effects; low; doses

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.

目的：研究辐射损伤细胞的信号体。 方法：将使用产生强有力的非靶向辐射反应的细胞系和活鱼来研究受辐射细胞和组织产生的信号的性质，并确定未受辐射但从受辐射细胞接收信号的细胞和生物体如何处理该信号。我们小组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有一个物理成分。我们将使用理论和实验方法来检验低能光子参与的假设。 重要性和新奇：自从人们接受可以在未受辐照的细胞或受辐照细胞的远缘后代中测量非靶向效应以来，关于这些效应与放射生物学和辐射防护的相关性的讨论不断发展，因为它们增加了辐射反应的复杂性，并使结果不像在“旧规则”下那样可预测。重要的是要考虑实际应用的相关性，如辐射防护和放射治疗，但也感兴趣的是它们如何影响生物进化和适应的想法。我们小组的重要例子是：（i）数据显示，旁观者机制在细胞中要么开启要么关闭，而且“开启”阈值似乎处于非常低的剂量（毫戈瑞范围），（ii）表明适应性反应不仅在邻近细胞中诱导，而且在接收旁观者信号的生物体中诱导的数据，以及（iii）数据表明，长期暴露于α或γ辐射会导致生物体产生复杂的反应，这种反应可能是适应性和保护性的。考虑这些信号传导机制也可能有益于癌症生物学，为癌细胞社会群体的调节以及这些群体如何与宿主相互作用提供新的见解。该建议旨在澄清信号的性质，并确定这些影响如何导致组织各级的适应性变化。