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

Abstract 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 dev...

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Veröffentlicht in:Journal of radiation research 2017-05, Vol.58 (3), p.273-280
Hauptverfasser: Iizuka, Daisuke, Yoshioka, Susumu, Kawai, Hidehiko, Izumi, Shunsuke, Suzuki, Fumio, Kamiya, Kenji
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Sprache:eng
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Zusammenfassung:Abstract 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.
ISSN:0449-3060
1349-9157
DOI:10.1093/jrr/rrw112