Short-term metabolic disruptions in urine of mouse models following exposure to low doses of oxygen ion radiation

Abstract

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 (¹⁶O) 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 ¹⁶O (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.

Keywords:

• Cosmic radiation
• high-LET charged particle radiation
• oxygen ion radiation
• metabolic dysregulation
• urinary metabolites

Data availability statement

The data that support the findings of this study are openly available in Dryad Digital Repository at https://doi.org/10.5061/dryad.gb5mkkwn9.

Additional information

Funding

This study was supported by the National Space Biomedical Research Institute [RE03701 through NCC 9–58] and 1U01AI133561-01 funding from NIH/NIAID to AKC and National Institute of Allergy and Infectious Diseases. The authors would like to acknowledge the Metabolomics Shared Resource in Georgetown University (Washington, DC, USA) which is partially supported by NIH/NCI/CCSG grant P30-CA051008.