title: 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 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.
authors.affiliation: Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.|Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-2, Kagamiyama, Higashi-Hiroshima 739-8511, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iizuka
authors.affiliation: Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Yoshioka
authors.affiliation: Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.|Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-2, Kagamiyama, Higashi-Hiroshima 739-8511, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kawai
authors.affiliation: Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Izumi
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-3-2, Kagamiyama, Higashi-Hiroshima 739-8511, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D005583:Fourier Analysis; D005720:Gamma Rays; D008297:Male; D055442:Metabolome / Q000528:radiation effects; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008970:Molecular Weight; D011827:Radiation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014556:Urine / Q000737:chemistry*
keywords: 1-methylhistamine; biodosimetry; metabolomics analysis; urine