title: Space radiation-associated lung injury in a murine model.
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 (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si 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 (56)Fe or (28)Si 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 dose-dependent, 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.
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; melpo@mail.med.upenn.edu.
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Pietrofesa
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania;
authors.forename: Evguenia
authors.initials: E
authors.lastname: Arguiri
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Division, Indiana University School of Medicine, Indianapolis, Indiana;
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Schweitzer
authors.affiliation: Department of Medicine University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Berdyshev
authors.affiliation: University of Texas Medical Branch (UTMB), Galveston, Texas;
authors.forename: Maureen
authors.initials: M
authors.lastname: McCarthy
authors.affiliation: University of Texas Medical Branch (UTMB), Galveston, Texas;
authors.forename: Astrid
authors.initials: A
authors.lastname: Corbitt
authors.affiliation: Oak Ridge Associated Universities, NASA Postdoctoral Program, Moffett Field, California;
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Alwood
authors.affiliation: University of Texas Medical Branch (UTMB), Galveston, Texas;
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Yu
authors.affiliation: NASA Ames Research Center, Moffett Field, California;
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Globus
authors.affiliation: Department of Pathology, Jefferson University Hospital, Philadelphia, Pennsylvania; and.
authors.forename: Charalambos C
authors.initials: CC
authors.lastname: Solomides
authors.affiliation: University of Texas Medical Branch (UTMB), Galveston, Texas;
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ullrich
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Division, Indiana University School of Medicine, Indianapolis, Indiana; Richard L. Roudebush VA Medical Center, Indianapolis, Indiana.
authors.forename: Irina
authors.initials: I
authors.lastname: Petrache
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D049109:Cell Proliferation; D003359:Cosmic Radiation / Q000009:adverse effects*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000473:pathology; D055370:Lung Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008297:Male; D008809:Mice, Inbred C3H; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood; D011014:Pneumonia / Q000097:blood / Q000150:complications / Q000473:pathology; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D010100:Oxygen
keywords: 28Si; 56Fe; emphysema; gamma radiation; hypoxemia; inflammation; lung injury; oxidative stress; protons; senescence