In the last decade, geopolitical instability across the globe has increased the risk of a large-scale radiological event, when radiation biomarkers would be needed for an effective triage of an irradiated population. Ionizing radiation elicits a complex response in the proteome, genome, and metabolome and hence can be leveraged as rapid and sensitive indicators of irradiation-induced damage. We analyzed the plasma of total-body irradiated (TBI) leukemia patients (n = 24) and nonhuman primates (NHPs; n = 10) before and 24 h after irradiation, and we performed a global metabolomic study aiming to provide plasma metabolites as candidate radiation biomarkers for biological dosimetry. Peripheral blood samples were collected according to the appropriate ethical approvals, and metabolites were extracted and analyzed by liquid chromatography mass spectrometry. We identified an array of metabolites significantly altered by irradiation, including bilirubin, cholesterol, and 18-hydroxycorticosterone, which were detected in leukemia patients and NHPs. Pathway analysis showed overlapping perturbations in steroidogenesis, porphyrin metabolism, and steroid hormone biosynthesis and metabolism. Additionally, we observed dysregulation in bile acid biosynthesis and tyrosine metabolism in the TBI patient cohort. This investigation is, to our best knowledge, among the first to provide valuable insights into a comparison between human and NHP irradiation models. The findings from this study could be leveraged for translational biological dosimetry.

Armed Forces Radiobiology Research Institute Uniformed Services University of the Health Sciences Bethesda MD 20814 USA

Biomedical Research Centre University Hospital Hradec Králové 500 05 Hradec Králové Czech Republic

Department of Biochemistry Molecular and Cellular Biology Georgetown University Medical Center Washington DC 2057 USA

Department of Haematology and Blood Transfusion University Hospital Na Bulovce 128 00 Prague Czech Republic

Department of Molecular Biology and Pathology Faculty of Military Health Sciences University of Defence 500 01 Hradec Králové Czech Republic

Department of Oncology Lombardi Comprehensive Cancer Center Georgetown University Medical Center Washington DC 20057 USA

Department of Radiobiology Military Faculty of Medicine University of Defence 662 10 Brno Czech Republic

Division of Radioprotectants Department of Pharmacology and Molecular Therapeutics F Edward Hébert School of Medicine Uniformed Services University of the Health Sciences Bethesda MD 20814 USA

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