Metabolic Characteristics Associated With Ionizing Radiation Injury Of Total Body Irradiation Patients

Background and purpose:The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of rapid,accurate and noninvasive methods for evaluation of ionizing radiation injury.There is growing concern about radiation injury biomarkers based on metabolomics in radiobiology.However,most of studies mainly focus on animal's models at present,lacking of studies and validation in humans.In this study,hematopoietic stem cell transplantation patients with total body irradiation(TBI)pretreatment were used to investigate the effect of ionizing radiation on urine and plasma metabolites,utilizing a pseudotargeted method based on gas chromatography-mass spectrometry(GC-MS)and liquid chromatography-mass spectrometry(LC-MS).The differential metabolic features associated with radiation injury were selected and the involved metabolic pathways were explored.The results provide experimental basis for the discovery and validation of radiation injury biomarkers as well as for the revealing the radiation injury and repair mechanisms.1.Selected reaction monitoring(SRM)based pseudo-targeted metabolomics methods of gas chromatography-mass spectrometry(GC-MS)and liquid chromatography-mass spectrometry(LC-MS)were developed.The intra-day,inter-day precision and reproducibility were investigated.The results showed that the methods are stable and reliable for large-scale analysis of urine samples.2.The changes of metabolites in urine of TBI patients were investigated by using the established pseudo-targeted metabolomics methods.One-way reapeated Anova analysis was used to screen urine metabolic features associating with radiation injury,and sex differences were analyzed.The metabolic characteristics of urinary samples showed that ionizing radiation could lead to disturbance of energy metabolism including amino acid metabolism,purine metabolism,glycolysis pathway,TCA cycle and fatty acid ? oxidation.In addition,some metabolic features had sex-specific responses after radiation exposure.Combined with multivariate analysis,seventeen potential urinary biomarkers that could distinguish between low and high doses samples were screened.3.The plasma metabolic changes of TBI patients were investigated by using pseudo-targetd metabolic method based on LC-MS.The non-parametric paired test was chosen to select metabolic features associated with radiation injury.Moreover,the involved main metabolic pathways and metabolic correlation network were explored.Moreover,metabolic related networks revealed that the correlation was significantly enhanced among the metabolites involved in amino acids metabolism,lipid metabolism and microbial metabolism after total body irradiation.