A Serum Small Molecule Biosignature of Radiation Exposure from Total Body Irradiated Patients

Abstract

The potential for radiological accidents and nuclear terrorism has increased the need for the development of new rapid biodosimetry methods. In addition, in a clinical setting the issue of an individual’s radiosensitivity should be taken into consideration during radiotherapy. We utilized metabolomics and lipidomics to investigate changes of metabolites in serum samples following exposure to total body ionizing radiation in humans. Serum was collected prior to irradiation, at 3–8 h after a single dose of 1.25–2 Gy, and at 24 h with a total delivered dose of 2–3.75 Gy. Metabolomics revealed perturbations in glycerophosphocholine, phenylalanine, ubiquinone Q2, and oxalic acid. Alterations were observed in circulating levels of lipids from monoacylglycerol, triacylglycerol, phosphatidylcholine, and phosphatidylglycerol lipid classes. Polyunsaturated fatty acids were some of the most dysregulated lipids, with increased levels linked to proinflammatory processes. A targeted metabolomics approach for eicosanoids was also employed. The results showed a rapid response for proinflammatory eicosanoids, with a dampening of the signal at the later time point. Sex differences were observed in the markers from the untargeted approach but not the targeted method. The ability to identify and quantify small molecules in blood can therefore be utilized to monitor radiation exposure in human populations.

Early metabolic characterization of brain tissues after whole body radiation based on gas chromatography–mass spectrometry in a rat model

“…It has been reported that levels of AA and eicosanoids derived from AA increase in the serum of mice at 24 h following irradiation (Laiakis et al, ). Moreover, a striking increase in free fatty acids including AA, Ole and pro‐inflammatory eicosanoids was observed in total body‐irradiated patients (Laiakis et al, ). These eicosanoids by the cytochrome P‐450 enzymatic pathway are the primary metabolites from AA in the brain (Roman, ) and play important roles in renal and cardiovascular functions.…”

“…As an environmental stimulus, radiation exposure inevitably causes perturbations of metabolic response. Multiple previous studies based on metabolomics have been applied for assessing ionizing radiation exposure from rodents, nonhuman primates and total body‐irradiated patients (Coy et al, ; Laiakis et al, ; Pannkuk, Laiakis, Fornace, Fatanmi, & Singh, ). Because of the easy sample collection and less invasive nature, biofluids (urine, plasma and serum) are the main sources of biomarkers for radiation exposure.…”

Metabolomics in Radiation Biodosimetry: Current Approaches and Advances

“…Indeed, blood metabolomic markers may be able to distinguish the type of radiation one is exposed to, as was found when mice were exposed to X-ray vs. neutron radiation [36]; or determine specific organ injury, as Jones et al found when studying small intestine tissue metabolites compared to plasma metabolites of mice exposed to TBI [114]. Importantly, some metabolite signatures, including increases in polyunsaturated fatty acid-containing lipids, have been consistently found across mice [115,116], NHPs [26,117], and humans [118], over a range of radiation doses. Not only is blood a useful biosample to assess acute radiation response, but can also be used to predict delayed effects of acute radiation exposure (DEARE).…”

“…Thus, it is extremely important to collect samples longitudinally to track these functional metabolomic changes, in order to determine progression of injury and timepoints with greatest diagnostic and prognostic accuracy [123]. Temporal changes in metabolomic biomarkers can also vary depending on sex [22,118,126,154], as discussed earlier. Additionally, temporal metabolomic changes and diagnostic/prognostic accuracy of metabolomic markers may vary depending on the sample type [127,140], which is also a factor to consider when designing biomarker discovery and validation studies.…”

Cellular and Molecular Effects of Ionizing Radiation

“…Hücreyi Sorumlu Yazar / Corresponding Author: Yaşar Aysun MANİSALIGİL, aysun.manisaligil@deu.edu.tr Geliş Tarihi / Received: 05.09.2018 Kabul Tarihi / Accepted: 25.10.2018 Bu çalışma, II. Uluslararası Katılımlı Radyasyondan Korunma Kongresi'nde (23)(24)(25) Kasım 2017, Ankara) sözlü bildiri olarak sunulmuştur.…”