Neutron-induced Carcinogenic Effects (NICE)-an examination of the biophysics underlying radiation carcinogenesis using neutrons

中子诱发的致癌效应（NICE）——使用中子检查辐射致癌作用的生物物理学

• 批准号: RGPIN-2021-02749
• 负责人: Kildea, John
• 金额: $ 2.48万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761826
• 关键词: Neutron; induced; Carcinogenic; Effects; NICE

Ionizing radiation is a potent carcinogen that is encountered in our natural and artificial environments. We cannot avoid it. Thankfully, radiological protection laws and regulations protect individuals from the carcinogenic risk that excess ionizing radiation poses. However, while these measures guard against unjustified use of radiation, they cannot protect three distinct populations: (1) radiotherapy and radiology patients, for whom the out-of-field radiation dose is limited only by the justification (i.e. prescription) of the medical practitioner, (2) astronauts travelling in deep space who will be exposed to a low-dose smorgasbord of cosmic rays, and (3) individuals who may be exposed to unknown radiation levels in the unlikely, but not impossible, event of a nuclear accident, atomic bomb, or terrorist attack involving an improvised nuclear device. Accordingly, any improvement to our understanding of radiation-induced carcinogenesis will help clinicians, policy-makers, and first responders make informed decisions to protect these populations. In our research program, we are working to improve our understanding of the etiology of radiation-induced cancer by studying neutrons. We are focusing on neutrons because their effectiveness at causing cancer is known to be energy-dependent, which suggests an underlying energy-dependent DNA-damage mechanism. We are examining the biophysics involved using a combination of neutron spectral measurements (physics), Monte Carlo modelling (physics and chemistry), and cell irradiation experiments (biology). Specifically, we are aiming to predict the relative mutation signatures that neutrons of different energies will induce in the DNA of irradiated cells. Using the neutron sources available to us (radiotherapy accelerators, reactors, and neutron generators), we will experimentally test our predictions by irradiating cells in vitro and examining the mutational signatures induced in them using a novel single-cell DNA sequencing protocol that our group is pioneering. Our combination of modelling and experiment will provide us with unique insight into the biophysical action of ionizing radiation. The results of our research will be of interest to researchers in the radiation medicine, space travel, and nuclear emergency preparedness fields, and our program will provide a rich multi-disciplinary environment to train the next generation of Canadian radiation biology and radiation protection researchers.

电离辐射是一种强烈的致癌物质，在我们的自然和人工环境中都会遇到。我们无法避免它。值得庆幸的是，放射防护法律和法规保护个人免受过量电离辐射造成的致癌风险。然而，虽然这些措施防止不合理地使用辐射，但它们不能保护三个不同的群体：(1)放射治疗和放射科患者，对他们来说，场外辐射剂量仅受医生的正当理由(即处方)的限制，(2)在深空旅行的宇航员将暴露在低剂量的宇宙射线自助餐中，以及(3)在发生核事故、原子弹或涉及简易核装置的恐怖袭击时可能暴露于未知辐射水平的个人。因此，我们对辐射致癌认识的任何改进都将有助于临床医生、政策制定者和急救人员做出明智的决定，以保护这些人群。在我们的研究计划中，我们正在努力通过研究中子来提高我们对辐射诱发癌症的病因学的理解。我们之所以关注中子，是因为众所周知，中子致癌的有效性依赖于能量，这表明潜在的依赖能量的DNA损伤机制。我们正在使用中子光谱测量(物理学)、蒙特卡罗模拟(物理学和化学)和细胞辐照实验(生物学)相结合的方法来检验所涉及的生物物理学。具体地说，我们的目标是预测不同能量的中子将在受辐射细胞的DNA中诱导的相对突变特征。使用我们可用的中子源(放射治疗加速器、反应堆和中子发生器)，我们将通过照射体外细胞并使用我们团队首创的新型单细胞DNA测序方案检查它们诱导的突变特征，来实验验证我们的预测。我们的建模和实验的结合将为我们提供对电离辐射的生物物理行为的独特见解。我们的研究成果将引起辐射医学、太空旅行和核应急准备领域的研究人员的兴趣，我们的计划将为培养下一代加拿大辐射生物学和辐射防护研究人员提供丰富的多学科环境。