Identification of odor biomarkers in irradiation injury urine based on headspace SPME-GC-MS

Purpose: The threat of population exposure to ionizing radiation is increasing rapidly worldwide. Such exposure, especially at high-dose, is known to cause acute radiation syndrome (ARS). Hence, it is necessary to develop specific and sensitive biomarkers to accurately diagnose radiation injury and evaluate medical countermeasures. Materials and methods: Caenorhabditis elegans (C. elegans), a model organism with a fine and sound olfactory system, was used to examine the odor of urine samples collected from irradiation-injured rats, and compared with those from un-irradiated control rats to investigate the 'special odor' of radiation injury. Subsequently, headspace SPME-GC-MS was applied for non-targeted metabolomic analysis of volatile organic compounds (VOCs) in urine, with the aim to discover changes of small molecule metabolites and identify odor biomarkers of irradiation injury. Results: C. elegans showed significant attraction to the urine of total body irradiation (TBI) rats compared with control rats, indicating that irradiation injury can emit 'special odor' and the metabolites in urine VOCs were changed. Using metabolomics based on headspace SPME-GC-MS for metabolic profiles analysis, we screened 63 differentially expressed metabolites. Among them, 10 metabolites including p-Cresol with excellent diagnostic ability were identified as odor biomarkers according to receiver operating characteristic (ROC) curve analysis. Conclusions: This study confirmed the 'special odor' induced by irradiation injury, and identified biomarkers through urine VOCs analysis for the first time, which can provide a novel approach and insight to evaluate irradiation injury noninvasively, accurately and conveniently. [GRAPHICS]