Date of Award

12-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Member

Dr. Delphine Dean, Committee Chair

Committee Member

Dr. Ted Bateman

Committee Member

Dr. Jiro Nagatomi

Committee Member

Dr. John DesJardins

Abstract

Bone loss has been identified as a characteristic response to radiation exposure in both clinical and space settings. One of the known long-term consequences of radiation treatment for cancer is increased risk of fracture due to declined bone health. Astronauts are also at risk, although the sources and total doses are much different than that of radiotherapy patients. The development of radiation protection countermeasures for long-term space missions requires a thorough understanding of the radiation's biological effects and the mechanisms behind them. The main objective of these studies is to further our understanding of the effect spaceflight relevant radiation has on bone in a well characterized animal model. Animal models are used extensively to study the effects of radiation, with mice being one of the most commonly used subjects. However, one consistent model does not exist across all studies; there is considerable variation in animal strain, sex, and age. In addition, the majority of studies examining radiation-induced bone loss have used doses exceeding what is expected for a long-term spaceflight mission. Lower doses have been used in some studies of heavier ions, but there is a significant lack of data for ions in the range between carbon and iron. The results of these studies develop a robust murine model for radiation-induced bone loss. The model was used to confirm that spaceflight relevant doses of protons have negative impacts on trabecular bone without regard to dose-rate and identify a novel anabolic effect to cortical bone. Additionally, a potential differential effect of low doses of heavy ions based on linear energy transfer (LET) was identified. Future studies should further investigate the mechanisms behind anabolic stimulation of osteoblasts at low doses and evaluate its potential as a countermeasure to reductions in bone strength due to radiation exposure. Additional data also needs to be collected to determine the full extent of the effect of LET on bone's response to radiation. The results will ultimately determine if a shift in the current model of how tissues respond to heavy ion radiation is required.

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