Differential mobility spectrometry-tandem mass spectrometry (DMS-MS/MS) uncovers the consequence of radiation exposure through the urinary acylcarnitine profile

• Online Access: http://hdl.handle.net/2047/D20316345

Abstract of Dissertation Nuclear events such as the Chernobyl power plant explosion of 1986 and the Fukushima accident in 2016 are constant reminders that society needs to be prepared for tragedy when it strikes. As a contribution toward the development of metabolomics-based radiation biodosimetry in human populations, we have developed a quantitative, high-throughput method for the analysis of urinary acylcarnitines, zwitterionic molecules that have been identified as biomarkers of radiation exposure. Differential mobility spectrometry is an analytical technique that separates molecules based on their size and shape. We coupled the Sciex SelexIon DMS with a QTRAP 5500 mass spectrometer and analyzed NHP urinary acetylcarnitine from male cohorts exposed to escalating doses of radiation. We observed biological levels ranging from 10 µM in the control group to 600 µM in the 10 Gy exposed group. Next, we chose to investigate the metabolic effects of radiation therapy in humans. Cancer patients underwent radiation treatment and their urine was collected. In total, nine urinary acylcarnitines were detected and quantified. Most acylcarnitine species were reduced at 6 hrs. post irradiation; however, only acetylcarnitine (C2:0-CN) and valerylcarnitine (C5:0-CN) recovered at 24 hrs. post irradiation. Three acylcarnitine species were not altered as a result of radiation treatment. Thus, the NHP and human data demonstrate the utility of FIA-DMS-MS/MS as a rapid, quantitative technique that can be applied toward the analysis of urinary biomarkers, and we believe that the findings from this research project will benefit the medical community, space research laboratories and disaster response groups.