Characterizing and Modeling the Biological Effects of Internal Radionuclide Exposure in Beagle Dogs

Copeland-Hardin, Letonia

doi:https://doi.org/10.21985/n2-cxfz-4d57

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Characterizing and Modeling the Biological Effects of Internal Radionuclide Exposure in Beagle Dogs

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The negative early and late health consequences from exposure to artificial sources of radiation are particularly apparent in victims of radiological emergencies who were diagnosed with cancer, radiation pneumonitis, among other conditions. The renaissance of nuclear energy, increased use of ionizing radiation in the medical field, and nuclear threats from enemy combatants have augmented concerns about hazards posed by radiation exposure. Studies directly comparing biological effects of internal radiation exposure and external beam exposure are limited. Furthermore, few recent studies focus on how internal radiation exposure via inhalation uniquely influences the pulmonary conditions as a group compared to non-pulmonary conditions despite the possibility of inhalation of radioactive fallout occurring during mass-casualty radiation events. Further elucidation of the biological effects of radiation exposure is important to fill the unmet need for more efficient biodosimetry, and machine learning tools to assist medical professionals with robust clinical decision-making during mass-casualty and radiological emergencies. Furthermore, studies investigating the harmful effects of radiation inform radiation protection standards developed by radiation regulatory bodies tasked with protecting the public from harmful levels of radiation. We utilized data and preserved tissues from dogs studied in the large-scale, lifespan studies conducted at the Inhalation Toxicology Research Institute (ITRI) from the 1960s-1990s. These resources allowed us to investigate the effects of inhaling β-particle emitting radionuclides in beagle dogs. Additionally, we completed initial steps for the development of robust tools to inform clinical decision-making during radiological emergencies. For example, we established X-ray fluorescence microscopy (XFM) as a viable method for future elemental, internal-radiation, biomarker discovery studies that are needed for developing novel, internal-radiation, biodosimetry assays. We completed an elementalomics analysis of canine, formalin-fixed, paraffin-embedded lung and tracheobronchial lymph node specimens from a dog that inhaled yttrium-90-containing microparticles from the ITRI lifespan beagle studies. Furthermore, we investigated the effects of inhaling radioactive microparticles on the mortality and occurrence of internal radiation-associated pulmonary conditions. These results supported the development of preliminary prognostic predictive model estimating the probability of pulmonary causes of death following inhalation of radionuclides that are nuclear fission byproducts. Our findings support ongoing efforts to advance current understanding and quantify risks associated with the use of ionizing radiation in the medical and energy sectors.

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