Monte Carlo-Modelled Dose Calibration Curves for use in Modernized Biodosimetry

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Biodosimetry (BD) is a tool for assessing the dose of ionizing radiation (IR) to which someone has been exposed. In order to understand the biological effects of this exposure, accurate physical dosimetry is required. Dose-response calibration curves (CC) are generated by irradiating blood samples with known doses and measuring the biological damage from each dose. This approach hinges on having well-calibrated physical dosimetry and methods to assess biological damage. Existing experimental methods measuring DNA damage from exposure to IR are well-established, but are slow and expensive. Currently the most sensitive of the assays has a lower limit of detection around 100 mSv. These methods need to be modernized to be specific to IR, to have excellent sensitivity to measure accurately and at lower doses and to be rapid for higher sample throughput. Monte Carlo (MC) modelling is a tool that can be used to simulate various radiation track structures and their implications for DNA damage including the resulting chromosomal geometry and aberrations. Software such as TOPAS-nBio provides a powerful toolkit to investigate radiation biology at sub-cellular scales and has greatly advanced this field of research. Accurate and informed BD requires CC that are representative of specific exposure scenarios of interest, including the relevant dose range, dose rate, and radiation type and quality. The long-term goals of this proposed research program are to (1) modernize BD methods using novel technologies and (2) establish validated, MC-based methods to model CC that could be transformed according to the exposure scenario. These modelled CC would be cost-effective, and would allow for more complex exposure scenarios such as protracted dose-rates and mixed beam exposures. Over the next five years, the short-term goals are to: (1) establish a validated MC model for DNA damage in blood cells, (2) validate a modelled CC for translocations as measured by FISH from X-ray exposures, (3) estimate a proof-of-concept dose for astronaut BD based on a space equivalent dose, and (4) model biological damage in the low dose regions (less than 100 mSv) to extrapolate CC. This work would take place in a government research laboratory at Health Canada (HC). Regarding feasibility of the proposed project, the necessary equipment is readily available and accessible for use. Furthermore, we are well-connected through collaborations to access other resources and centers of expertise as needed. HC has policies in place prioritizing healthy working environments, and promoting diversity and inclusivity in all aspects of our work. The funds requested would support this research program by focusing on the recruitment and training of highly qualified personnel. These results would help to understand the DNA damage mechanism from different radiation qualities at biologically relevant doses for both the space environment and the low-dose research programs.