Novel Double-Hit In Vitro Model of Oxidative Damage Associated with Cycling Exposure to Radiation and Hyperoxia Relevant To Space Travel

BACKGROUND Pre-breathe protocols in preparation for extravehicular activities (EVA) entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. Repeat cycling changes of oxygen levels may pose an added threat. Using a murine model of repeated hyperoxia and radiation exposure (double-hit), we have previously observed significant early and chronic lung inflammation, injury, and oxidative tissue damage. In order to explore the potential mechanism(s) behind the observed lung tissue damage, we developed a novel in vitro model of hyperoxia and radiation exposure in the context of evaluating countermeasures to lung cell damage associated with space flight. Our objective was to characterize the effects of repeated single and double-hit challenge on lung cells using a novel in vitro model of repeated exposure to radiation and hyperoxia. This is the first study of its kind evaluating lung cell damage relevant to space exploration in an in vitro model system.