Neutron-induced Carcinogenic Effects (NICE)-an examination of the biophysics underlying neutron carcinogenesis

我们的研究旨在提高我们对人体组织中中子剂量沉积的生物物理效应的理解。中子在太空、核电站、各种工业应用和放射治疗（RT）中都会遇到。辐射防护措施旨在保护人类免受中子（和其他形式的辐射）的危害。虽然这些措施通常是足够的，但它们不能保护接受RT的患者。在高能（>10 MeV）光子束和质子束RT过程中作为副产品产生的中子，即辐射，不能被屏蔽，因此暴露的患者容易受到辐射诱发的致癌作用。这种风险是众所周知的，也是普遍接受的，尽管人们对这种风险了解甚少。目前正在努力将质子束RT引入加拿大，使这个问题成为焦点。儿科患者被认为是质子RT的主要受益者，也是第二次恶性肿瘤的最大风险，这是由于不可避免的全身剂量的二次辐射，部分来自中子。 PI和他以前的学生Robert Maglieri最近的研究表明，美国制造的嵌套中子谱仪（Detec Inc.，加蒂诺，魁北克）可用于测量来自RT束的中子的能谱。我们的报告（Maglieri等人，2015年）首次在医用直线加速器的辐射场中使用这种有源中子探测器，为RT中的实际中子谱测量开辟了可能性。 根据我们的新测量技术，并受其激励，我们对中子的能量依赖性致癌潜力的理解的提高将使我们能够将物理测量的中子能谱转换为生物学上有意义的剂量估计。 一个切实可行的方法，以促进我们的基本生物物理学的能量依赖的潜在的中子致癌性的理解是检查，在宏观剂量和纳米剂量尺度，中子剂量沉积过程作为能量的函数。其他研究小组已经完成了这类工作，以研究光子和质子的辐射损伤。因此，我们提出了一个Monte Carlo轨道结构的中子剂量沉积在DNA尺度上的研究，再加上实际测量的中子谱和中子DNA损伤的细胞，在体外。我们可以利用蒙特卡罗专门知识、RT设备以及我们在安大略乔克河的加拿大核实验室的合作者的中子束和放射生物学设施。考虑到这一切，我们在测量中子能谱并将其转换为有生物意义的剂量估计方面具有独特的经验、设施和动机。缺少的是对中子的能量依赖性致癌潜力的理解。提高这种理解是我们所提出的研究的目标。

Our research aims to improve our understanding of the biophysical effects surrounding neutron dose deposition in human tissue. Neutrons are encountered in space, at nuclear power plants, in various industrial applications, and in radiation therapy (RT). Radiological protection measures are designed to protect human populations from the risk that neutrons (and other forms of radiation) pose. While these measures are generally adequate, they cannot protect patients undergoing RT. Neutrons that are generated as by-product, radiation during high-energy (>10 MeV) photon- and proton-beam RT, cannot be shielded and consequently exposed patients are susceptible to radiation-induced carcinogenesis. The risk is well known and generally accepted, although poorly understood. Efforts currently underway to introduce proton beam RT into Canada have brought the issue into focus. Paediatric patients who are considered the main beneficiaries of proton RT are also the most at risk for second malignancies resulting from the unavoidable whole body dose of secondary radiation that arises in part from neutrons. Recent research by the PI and his former student Robert Maglieri has demonstrated that the Canadian-made Nested Neutron Spectrometer (Detec Inc., Gatineau, Quebec) may be used to measure the energy spectra of neutrons from RT beams. Our report (Maglieri et al., 2015) into the first use of this active neutron detector in the radiation field of a medical linac has opened the possibility for practical neutron spectral measurements in RT. In light of, and motivated by, our new measurement technique, an improvement in our understanding of the energy-dependent carcinogenic potential of neutrons would allow us to convert our physically-measured neutron energy spectra into biologically-meaningful dose estimates. One practical way to advance our understanding of the fundamental biophysics underlying the energy-dependent carcinogenic potential of neutrons is to examine, at the macrodosimetric and nanodosimetric scales, neutron dose deposition processes as a function of energy. This type of work has been done by other groups to study radiation damage by photons and protons. We thus propose a Monte Carlo track structure study of neutron dose deposition at the DNA-scale coupled with actual measurements of neutron spectra and of neutron DNA damage in cells, in vitro. We have access to Monte Carlo expertise, RT equipment and to the neutron beams and radiobiological facilities of our collaborators at Canadian Nuclear Laboratories, Chalk River, Ontario. All considered, we are uniquely positioned with the experience, the facilities, and the motivation to measure neutron energy spectra and to convert them into biologically-meaningful dose estimates. Missing is an understanding of the energy-dependent carcinogenic potential of neutrons. Improving this understanding is the goal of our proposed research.