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

电离辐射是我们在自然和人工环境中遇到的一种强致癌物质。幸运的是，辐射防护法律和法规保护个人免受过量电离辐射带来的致癌风险。然而，虽然这些措施防止了不合理地使用辐射，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，其野外辐射剂量仅受理由限制（2）在深空旅行的宇航员，他们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、原子弹爆炸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，我们对辐射致癌作用的理解的任何改进都将有助于临床医生、决策者和第一反应者做出明智的决定，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，是因为它们致癌的有效性是依赖于能量的，这表明了一种潜在的依赖于能量的DNA损伤机制。我们正在研究的生物物理学涉及使用中子光谱测量（物理），蒙特卡罗建模（物理和化学），和细胞辐照实验（生物学）的组合。具体来说，我们的目标是预测不同能量的中子将在辐照细胞的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），我们将通过体外照射细胞并使用我们小组开创的新型单细胞DNA测序方案检查诱导的突变特征来实验性地测试我们的预测。我们的建模和实验相结合，将为我们提供独特的见解电离辐射的生物物理作用。我们的研究结果将感兴趣的辐射医学，太空旅行和核应急准备领域的研究人员，我们的计划将提供一个丰富的多学科环境，以培养加拿大辐射生物学和辐射防护研究人员的下一代。

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.