title: Urinary metabolic signatures and early triage of acute radiation exposure in rat model.
abstract: After a large-scale radiological accident, early-response biomarkers to assess radiation exposure over a broad dose range are not only the basis of rapid radiation triage, but are also the key to the rational use of limited medical resources and to the improvement of treatment efficiency. Because of its high throughput, rapid assays and minimally invasive sample collection, metabolomics has been applied to research into radiation exposure biomarkers in recent years. Due to the complexity of radiobiological effects, most of the potential biomarkers are both dose-dependent and time-dependent. In reality, it is very difficult to find a single biomarker that is both sensitive and specific in a given radiation exposure scenario. Therefore, a multi-parameters approach for radiation exposure assessment is more realistic in real nuclear accidents. In this study, untargeted metabolomic profiling based on gas chromatography-mass spectrometry (GC-MS) and targeted amino acid profiling based on LC-MS/MS were combined to investigate early urinary metabolite responses within 48 h post-exposure in a rat model. A few of the key early-response metabolites for radiation exposure were identified, which revealed the most relevant metabolic pathways. Furthermore, a panel of potential urinary biomarkers was selected through a multi-criteria approach and applied to early triage following irradiation. Our study suggests that it is feasible to use a multi-parameters approach to triage radiation damage, and the urinary excretion levels of the relevant metabolites provide insights into radiation damage and repair.
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren'ai Road 199, Suzhou 215123, P. R. China. wangchang177@126.com wangchang@suda.edu.cn.
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Applied Chemistry, Xi'an Jiaotong-Liverpool University, Suzhou Industrial Park Ren'ai Road 111, Suzhou 215123, P. R. China.
authors.forename: Kim Kt
authors.initials: KK
authors.lastname: Lau
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren'ai Road 199, Suzhou 215123, P. R. China. wangchang177@126.com wangchang@suda.edu.cn.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Applied Chemistry, Xi'an Jiaotong-Liverpool University, Suzhou Industrial Park Ren'ai Road 111, Suzhou 215123, P. R. China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Entomology and Nematology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA. junyang@ucdavis.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou Industrial Park Ren'ai Road 199, Suzhou 215123, P. R. China. wangchang177@126.com wangchang@suda.edu.cn.
authors.forename: Chang
authors.identifier: http://orcid.org/0000-0002-5390-9782
authors.initials: C
authors.lastname: Wang
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002853:Chromatography, Liquid; D002952:Citric Acid Cycle / Q000528:radiation effects; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D053858:Metabolic Networks and Pathways / Q000528:radiation effects; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D010758:Phosphorus / Q000378:metabolism; D000069079:Radiation Exposure; D011832:Radiation Injuries / Q000652:urine*; D051381:Rats
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D010758:Phosphorus