Metabolomic screening using ESI-FT MS identifies potential radiation-responsive molecules in mouse urine

The demand for establishment of high-throughput biodosimetric methods is increasing. our aim in this study was to identify low-molecular-weight urinary radiation-responsive molecules using electrospray ionization fourier transform mass spectrometry (esi-ft ms),and our final goal was to develop a sensitive biodosimetry technique that can be applied in the early triage of a radiation emergency medical system. we identified nine metabolites by statistical comparison of mouse urine before and 8 h after irradiation. time-course analysis showed that,of these metabolites,thymidine and either thymine or imidazoleacetic acid were significantly increased dose-dependently 8 h after radiation exposure; these molecules have already been reported as potential radiation biomarkers. phenyl glucuronide was significantly decreased 8 h after radiation exposure,irrespective of the dose. histamine and 1-methylhistamine were newly identified by ms/ms and showed significant,dose-dependent increases 72 h after irradiation. quantification of 1-methylhistamine by enzyme-linked immunosorbent assay (elisa) analysis also showed a significant increase 72 h after 4 gy irradiation. these results suggest that urinary metabolomics screening using esi-ft ms can be a powerful tool for identifying promising radiation-responsive molecules,and that urinary 1-methylhistamine is a potential radiation-responsive molecule for acute,high-dose exposure. © the author 2016. published by oxford university press on behalf of the japan radiation research society and japanese society for radiation oncology.