Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation.

Maryam Goudarzi,Albert Fornace,Siddheshwar Chauthe,Waylon Weber,David Brenner,Steven Strawn

doi:10.3390/ijms17050782

Abstract

With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs) and Strontium-90 (90Sr). The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation.

Highlights

In the current socio-political environment, there is increasing concern for improvised radiologic and nuclear devices
The principle component analysis (PCA) plot in Figure 1A shows that, while exposure to all four types of ionizing radiation (IR) cases above induced statistically significant and distinct perturbations in the overall urinary metabolomic signature in mice compared to that of the control mice, the differences in these perturbations in each exposure case is subtle as shown by the close clustering of the metabolomic profiles on the right hand side of the PCA plot
While we did not detect any statistically significant changes in the urinary excretion of citrulline at 4.4 Gy X-ray irradiation delivered at low dose rate (LDR) of 3.0 mGy/min, we did observe a statistically significant increase post 4.4 Gy X-ray irradiation at high dose rate (HDR) of 1.1 Gy/min (Figure 4)

Summary

Introduction

In the current socio-political environment, there is increasing concern for improvised radiologic and nuclear devices. Unplanned nuclear and radiological events are a source of concern with the recent Fukushima disaster as a reminder that we need better countermeasures. To this end, we have described a workflow for characterization of urinary and serum metabolomics signatures after exposure. While most of the effort in radiation biodosimetry.

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Discussion

Conclusion