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。在太空、核电站、各种工业应用和放射治疗(RT)中都会遇到中子。辐射防护措施旨在保护人类免受中子(和其他形式的辐射)带来的危险。虽然这些措施总体上是足够的，但它们不能保护接受RT的患者。在高能(&gt；10 MeV)光子和质子束放射治疗过程中产生的副产品中子不能被屏蔽，因此暴露在辐射中的患者容易发生辐射致癌。这种风险是众所周知的，也是普遍接受的，尽管人们对此知之甚少。目前正在进行的将质子束RT引入加拿大的努力使这一问题成为焦点。被认为是质子放射治疗的主要受益者的儿科患者也最有可能罹患第二种恶性肿瘤，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和他的前学生Robert Maglieri最近的研究表明，加拿大制造的嵌套中子谱仪(Detec Inc.，魁北克加蒂诺)可以用来测量RT束中中子的能谱。我们的报告(Maglieri等人，2015)首次在医用直线加速器的辐射领域使用这种有源中子探测器，为在RT中进行实际的中子光谱测量打开了可能性。 根据我们的新测量技术，并在其推动下，我们对中子致癌潜能的能量依赖的理解的改进将使我们能够将物理测量的中子能谱转换为具有生物意义的剂量估计。 提高我们对中子致癌潜能依赖能量的基本生物物理学基础的一种实用方法是在宏观剂量学和纳米剂量学尺度上研究中子剂量沉积过程作为能量的函数。其他研究小组在研究光子和质子对辐射的损害时，也做了这类工作。因此，我们提出了一种结合中子能谱和细胞内中子DNA损伤的实际测量的DNA尺度上的中子剂量沉积的蒙特卡罗径迹结构研究。我们可以使用蒙特卡罗专业技术、RT设备以及我们在安大略省Chalk River的加拿大核实验室的合作者的中子束和放射生物设施。综上所述，我们拥有独特的经验、设施和动机来测量中子能谱并将其转换为具有生物意义的剂量估计。MISTING是对中子的能量依赖致癌潜力的理解。提高这一认识是我们提出的研究目标。

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.