Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC 20057, USA.
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA.
Int J Mol Sci. 2021 Mar 17;22(6):3070. doi: 10.3390/ijms22063070.
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, O, and Fe) 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.
未来的太空任务将包括重返月球和往返火星的长时间深空任务。离开近地轨道提供的保护，宇航员将不可避免地暴露在更高的空间辐射累积剂量下，除此之外还有其他压力源，例如微重力。已知辐射和太空飞行都会影响免疫调节，目前还不清楚在深空环境中遇到的长期影响是否会对健康产生不利影响。在这项研究中，我们研究了雄性 C57BL/6 小鼠在暴露后 1、2 和 4 个月时，三种不同低剂量辐射（γ射线、O 和 Fe）在脾脏中的整体代谢的影响。在嘌呤代谢、三羧酸循环、脂肪酸、酰基辅酶 A 和氨基酸中，鉴定出了 40 种具有显著富集的代谢物。早期的扰动在 γ 辐照样本中更为明显，而随后的反应则偏向于高能粒子辐照组更为明显的反应。回归分析显示，鉴定出的脂肪酸的丰度与时间呈正相关，与 γ 射线呈负相关，而嘌呤的降解途径与时间呈正相关。综上所述，强烈表明存在线粒体牵连的可能性，并且在辐射暴露后，对 DNA 修复和核苷酸库可能产生长期影响。
