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Evaluation of lung damage related to extra‐vehicular activity (EVA) during space exploration using a novel murine and cell model of repeated double‐hit low‐level radiation and hyperoxia exposure
Author(s) -
Christofidou-Solomidou Melpo,
Pietrofesa Ralph A,
Dukes Floyd,
Tyagi Sonia,
Solomides Pantelis,
Arguiri Evguenia,
Solomides Charalambos C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1137.4
Subject(s) - hyperoxia , apoptosis , in vivo , inflammation , fibrosis , lung , oxidative stress , dna damage , andrology , dna fragmentation , medicine , bronchoalveolar lavage , pulmonary fibrosis , pathology , immunology , chemistry , biology , programmed cell death , biochemistry , dna , microbiology and biotechnology
Extra‐vehicular activities (EVA) during spaceflight missions expose crew members to challenges, such as hyperoxia and low levels of cosmic/galactic radiation that may present a threat to their health. Our objectives were to develop and characterize in vivo/in vitro models of similar double‐hit challenges. Mouse cohorts (n=10/group) were exposed to: a) normoxia; b) >95% O2 (O2); c) 0.25Gy gamma radiation (RAD); or d) a combination of O2 and RAD (O2+RAD). Challenge (O2 or RAD) was given 3X weekly for 1, 2 or 4 wks; 8‐hour hyperoxia was spanned by normoxic intervals. Lungs were evaluated for oxidative damage, inflammation, injury and fibrosis. In addition, mouse lung epithelial cells, exposed to similar O2 or RAD conditions were evaluated for apoptosis, DNA fragmentation and survival. After just 1 wk, all treatments resulted in significant mouse lung injury (p<0.05) evidenced by increased bronchoalveolar lavage protein levels and significant inflammation (p<0.003). O2 and O2+RADexposed mice had higher oxidative tissue damage (p<0.01) by 2 wks. Elevated lung tissue fibrosis was detected (p<0.04) as early as 1 wk. Epithelial cells exposed to all conditions had marked increases in apoptosis and DNA damage, and reduced survival. In conclusion, we have developed and characterized an EVA‐related in vivo/in vitro model of repeated low‐level radiation and hyperoxia. Funded by: NIH/NCI, NASA (MCS)