Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules

Abstract

Purpose: Exposure of the general population to ionizing radiation has increased in the past decades, primarily due to long distance travel and medical procedures. On the other hand, accidental exposures, nuclear accidents, and elevated threats of terrorism with the potential detonation of a radiological dispersal device or improvised nuclear device in a major city, all have led to increased needs for rapid biodosimetry and assessment of exposure to different radiation qualities and scenarios. Metabolomics, the qualitative and quantitative assessment of small molecules in a given biological specimen, has emerged as a promising technology to allow for rapid determination of an individual’s exposure level and metabolic phenotype. Advancements in mass spectrometry techniques have led to untargeted (discovery phase, global assessment) and targeted (quantitative phase) methods not only to identify biomarkers of radiation exposure, but also to assess general perturbations of metabolism with potential long-term consequences, such as cancer, cardiovascular, and pulmonary disease.

Conclusions: Metabolomics of radiation exposure has provided a highly informative snapshot of metabolic dysregulation. Biomarkers in easily accessible biofluids and biospecimens (urine, blood, saliva, sebum, fecal material) from mouse, rat, and minipig models, to non-human primates and humans have provided the basis for determination of a radiation signature to assess the need for medical intervention. Here we provide a comprehensive description of the current status of radiation metabolomic studies for the purpose of rapid high-throughput radiation biodosimetry in easily accessible biofluids and discuss future directions of radiation metabolomics research.

Keywords:

• Ionizing radiation
• metabolomics
• lipidomics
• biofluids
• rapid biodosimetry
• radiation signatures

Acknowledgements

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would also like to thank Bill Morgan for his countless support and encouragement, and most importantly his friendship throughout the years.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This work was funded by the National Institutes of Health (National Institute of Allergy and Infectious Diseases) grant U19 AI067773 (P.I. David J. Brenner, performed as part of Columbia University Center for Medical Countermeasures against Radiation) and grant 1R01AI101798 (P.I. Albert J. Fornace, Jr). Dr Pannkuk was supported by the training grant in the Tumor Biology Program 5T32CA9686-20.