Space radiation-associated lung injury in a murine model

Melpo Christofidou-Solomidou, Ralph A. Pietrofesa, Evguenia Arguiri, Kelly S. Schweitzer, Evgeny V. Berdyshev, Maureen McCarthy, Astrid Corbitt, Joshua S. Alwood, Yongjia Yu, Ruth K. Globus, Charalambos C. Solomides, Robert L. Ullrich, Irina Petrache

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to 137Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u 56Fe ions, or 350 MeV/u 28Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy 56Fe or 28Si ions markedly decreased sphingosine-1-phosphate levels and Akt-and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dosedependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions.

Original languageEnglish (US)
Pages (from-to)L416-L428
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume308
Issue number5
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Si
  • Fe
  • Emphysema
  • Gamma radiation
  • Hypoxemia
  • Inflammation
  • Lung injury
  • Oxidative stress
  • Protons
  • Senescence

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Christofidou-Solomidou, M., Pietrofesa, R. A., Arguiri, E., Schweitzer, K. S., Berdyshev, E. V., McCarthy, M., Corbitt, A., Alwood, J. S., Yu, Y., Globus, R. K., Solomides, C. C., Ullrich, R. L., & Petrache, I. (2015). Space radiation-associated lung injury in a murine model. American Journal of Physiology - Lung Cellular and Molecular Physiology, 308(5), L416-L428. https://doi.org/10.1152/ajplung.00260.2014