TY - JOUR
T1 - Effects of low dose space radiation exposures on the splenic metabolome
AU - Laiakis, Evagelia C.
AU - Shuryak, Igor
AU - Deziel, Annabella
AU - Wang, Yi Wen
AU - Barnette, Brooke L.
AU - Yu, Yongjia
AU - Ullrich, Robert
AU - Fornace, Albert J.
AU - Emmett, Mark
N1 - Funding Information:
Funding: This work was partially supported by NASA grant NNX15AD65G (P.I. Mark R. Emmett). The project described above was also supported by Award Number P30 CA051008 (P.I. Louis Weiner) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The Radiation Effects Research Foundation (RERF), Hiroshima, and Nagasaki, Japan, is a public interest foundation funded by the Japanese Ministry of Health, Labor and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DEHS0000031 to the National Academy of Sciences. The views of the authors do not necessarily reflect those of the two governments. Additionally, this research was partially supported by NASA/Texas Space Grant Consortium Fellowship (BLB), and Shirley Patricia Parker and Katherina Siebert Award for Excellence in Oncologic Scholarship (BLB).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/3/2
Y1 - 2021/3/2
N2 - Future space missions will include a return to the Moon and long duration deep space roundtrip missions to Mars. Leaving the protection that Low Earth Orbit provides will unavoidably expose astronauts to higher cumulative doses of space radiation, in addition to other stressors, e.g., microgravity. Immune regulation is known to be impacted by both radiation and spaceflight and it remains to be seen whether prolonged effects that will be encountered in deep space can have an adverse impact on health. In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays,16O, and56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.
AB - Future space missions will include a return to the Moon and long duration deep space roundtrip missions to Mars. Leaving the protection that Low Earth Orbit provides will unavoidably expose astronauts to higher cumulative doses of space radiation, in addition to other stressors, e.g., microgravity. Immune regulation is known to be impacted by both radiation and spaceflight and it remains to be seen whether prolonged effects that will be encountered in deep space can have an adverse impact on health. In this study, we investigated the effects in the overall metabolism of three different low dose radiation exposures (γ-rays,16O, and56Fe) in spleens from male C57BL/6 mice at 1, 2, and 4 months after exposure. Forty metabolites were identified with significant enrichment in purine metabolism, tricarboxylic acid cycle, fatty acids, acylcarnitines, and amino acids. Early perturbations were more prominent in the γ irradiated samples, while later responses shifted towards more prominent responses in groups with high energy particle irradiations. Regression analysis showed a positive correlation of the abundance of identified fatty acids with time and a negative association with γ-rays, while the degradation pathway of purines was positively associated with time. Taken together, there is a strong suggestion of mitochondrial implication and the possibility of long-term effects on DNA repair and nucleotide pools following radiation exposure.
KW - Immune
KW - Metabolism
KW - Mitochondria
KW - Space radiation
KW - Spleen
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U2 - 10.3390/ijms22063070
DO - 10.3390/ijms22063070
M3 - Article
C2 - 33802822
AN - SCOPUS:85102580576
SN - 1661-6596
VL - 22
SP - 1
EP - 16
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
M1 - 3070
ER -