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Astronauts embarking on deep space missions are at high risk of long-term exposure to low doses of high linear energy transfer (LET) radiation, which can contribute to the development of cancer and multiple degenerative diseases. However, long term effects of exposure to low doses of high LET radiation in plasma metabolite profiles have not been elucidated. We utilized an untargeted metabolomics and lipidomics approach to analyze plasma obtained from adult male Long Evans rats to determine the longitudinal effects of low-dose proton and low-dose oxygen ion whole-body irradiation on metabolic pathways. Our findings reveal that radiation exposure induced modest changes in the metabolic profiles in plasma, 7 months after exposure. Furthermore, we identified some common metabolite dysregulations between protons and oxygen ions, which may indicate a similar mechanism of action for both radiation types.

Molecular alterations as a result of exposure to low doses of high linear energy transfer (LET) radiation can have deleterious short- and long-term consequences on crew members embarking on long distance space missions. Oxygen ions ( 16 O) are among the high LET charged particles that make up the radiation environment inside a vehicle in deep space. We used mass spectrometry-based metabolomics to characterize urinary metabolic profiles of male C57BL/6J mice exposed to a single dose of 0.1, 0.25 and 1.0 Gy of 16 O (600 MeV/n) at 10 and 30 days post-exposure to delineate radiation-induced metabolic alterations. We recognized a significant down regulation of several classes of metabolites including cresols and tryptophan metabolites, ketoacids and their derivatives upon exposure to 0.1 and 0.25 Gy after 10 days. While some of these changes reverted to near normal by 30 days, some metabolites including p-Cresol sulfate, oxalosuccinic acid, and indoxylsulfate remained dysregulated at 30 days, suggesting long term prognosis on metabolism. Pathway analysis revealed a long-term dysregulation in multiple pathways including tryptophan and porphyrin metabolism. These results suggest that low doses of high-LET charged particle irradiation may have long-term implications on metabolic imbalance.