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

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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.