Journal Article

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

Daisuke Iizuka, Susumu Yoshioka, Hidehiko Kawai, Shunsuke Izumi, Fumio Suzuki and Kenji Kamiya

in Journal of Radiation Research

Volume 58, issue 3, pages 273-280
Published in print May 2017 | ISSN: 0449-3060
Published online December 2016 | e-ISSN: 1349-9157 | DOI: https://dx.doi.org/10.1093/jrr/rrw112
Metabolomic screening using ESI-FT MS identifies potential radiation-responsive molecules in mouse urine

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  • Clinical Genetics
  • Molecular Biology and Genetics
  • Epidemiology
  • Radiology
  • Nuclear Chemistry, Photochemistry, and Radiation

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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.

Keywords: biodosimetry; metabolomics analysis; urine; 1-methylhistamine

Journal Article.  3469 words.  Illustrated.

Subjects: Clinical Genetics ; Molecular Biology and Genetics ; Epidemiology ; Radiology ; Nuclear Chemistry, Photochemistry, and Radiation

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