Plasma Metabolic Characteristics Of Ionizing Radiation Injury Based On Metabolomics

After a large-scale radiological incident,an accurate,rapid biodosimetry is the basis of the rapid radiation triage for the exposed wounded.For the traditional biodosimetry,there are obvious drawbacks not only in the dose-response and time-response,but also in the rapidness.Therefore,the study on the dose assessment based on the panel of markers has drawn increasing attention.In this paper,Wistar rats and clinical patients with total body irradiation(TBI)were used to investigate the effect of ionizing radiation on plasma metabolites.The characteristic metabolites were identified and the main involved metabolic pathways were discussed.For the convenient clinical application,a panel of markers was selected by combining data statistical methods and diagnostic performance was evaluated in the rat model.Our data suggested that plasma metabolite levels can potentially be used to estimate radiation doses and reveal metabolic perturbations associated with radiation damage.1.The pseudo-targeted metabolomics based on GC-MS and LC-MS were established.The reproducibility of plasma sample preparations,the initial stability of the instrument and the intra-day and inter-day precision were investigated.The results showed the analytical methods had high repeatability,stability and reliability and were suitable for large scale analysis of plasma samples.2.By combining the pseudo-targeted metabolomics based on GC-MS and the plasma amino acid target analysis based on HPLC-MS,the plasma metabolic changes were determined in different time points after radiation.Then the characteristic metabolites were identified by combing multiple data statistical methods and pattern recognition methods and involving main metabolic pathways were discussed.For the convenient clinical application,the panel of markers associated with radiation injury was selected through multiple data statistical methods and was applied to radiation injury triage.3.The plasma metabolic changes of TBI patients by using pseudo-targetd metabolic method based on GC-MS.The non-parametric paired test was chosen to select characteristic metabolites associated with radiation injury.Moreover,the involving main metabolic pathways and network diagram were conducted.The results showed that there was similar metabolic phenotype in human and rodents following irradiation and some markers associated radiation injury are common in different species.