Goodarzi, AaronPearson, Dustin Daniel2021-05-172021-05-172021-05-11Pearson, D. D. (2021). An Analysis of Alpha Particle Radiation Exposure from the Population Level to the Biological Consequences (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/113428Lung cancer accounts for 38% of North American cancer related deaths and is the 7th leading cause of cancer related deaths for never-smokers. Radon (222Rn) gas inhalation is the 2nd leading cause of lung cancer in Canada and is the primary source of ionizing radiation (IR) exposure for most humans globally. Radioactive radon is an odorless, tasteless and colourless gas generated by the decay series of soil radionuclides including radium, thorium and uranium. Decaying 222Rn emits alpha particles, a type of high Linear Energy Transfer (LET) IR that, when contacting biological material, will induce complex and clustered DNA damage that is extremely difficult for human cells to repair accurately or quickly, increasing the risk of cancer-causing genetic mutations. The ability to study alpha particles has been limited and therefore it is still unclear as to how a cell repairs high LET-induced DNA damage. Radon is often captured, contained, and concentrated to hazardous levels within our built environment and, importantly, exposure to radon is increasing in many regions. Indeed, 21st-century North American residential properties contain historic radon highs, although the reasons for this are unclear. To address this, I analyzed 250,000+ real-time radon data points and 20,000+ long-term radon readings linked to residential property metrics. I conclude that alpha particle exposure from radon is occurring at doses and dose rates of serious risk to humans, and which correspond to verified cancer-causing radon exposures in mammals. Further to this, Canadians most at risk for high radon exposure are i) younger, ii) more likely to live in newer residential properties and iii) more likely to be starting parenthood. I find that Canadian properties most associated with high radon were single detached, large (>1750 sq. ft.), newer properties, with newer, more glazed windows and were home to people who do not open their windows regularly. Using multivariate analysis, I present new models useful to predict high and low radon in the Canadian residential environment and better understand particle IR exposure at population level. To understand the biological consequences of radon, I have helped to develop a new, high-throughput alpha particle irradiation system. Using this system, I identify functional interactions between the SNM1A and SNM1C/Artemis nucleases during repair of particle-induced complex DNA damage lesions. Using biology and biochemistry, I present evidence that supports the hypothesis that SNM1C functions to resolve DNA interstrand crosslink clustered together with DNA double strand breaks. My work is transdisciplinary: I have generated mechanistic insight in particle radiobiology, developed new technology that resolves long-standing logistical barriers, and I have built population-level data with implications to public health in terms of identifying at risk populations for radon exposure, and building practices relevant to engineering out radon exposure in the future.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.RadonRadiationDNA RepairSNM1 NucleasesClustered DNA damageComplex DNA damageLung CancerLinear Energy TransferHigh ThroughputAlpha ParticleBuilt EnvironmentBiologyBiology--CellBiology--MolecularBiochemistryChemistry--Radiationdoctoral thesis10.11575/PRISM/38875