Abstract
Triage and medical intervention strategies for unanticipated exposure during a radiation incident benefit from the early, rapid and accurate assessment of dose level. Radiation exposure results in complex and persistent molecular and cellular responses that ultimately alter the levels of many biological markers, including the metabolomic phenotype. Metabolomics is an emerging field that promises the determination of radiation exposure by the qualitative and quantitative measurements of small molecules in a biological sample. This review highlights the current role of metabolomics in assessing radiation injury, as well as considerations for the diverse range of bioanalytical and sampling technologies that are being used to detect these changes. The authors also address the influence of the physiological status of an individual, the animal models studied, the technology and analysis employed in interrogating response to the radiation insult, and variables that factor into discovery and development of robust biomarker signatures. Furthermore, available databases for these studies have been reviewed, and existing regulatory guidance for metabolomics are discussed, with the ultimate goal of providing both context for this area of radiation research and the consideration of pathways for continued development.
Highlights
There is currently an urgent, unmet need for biodosimetry tests to detect radiation exposure levels, to be deployed in the event of a large-scale nuclear incident, and to monitor injury progression and recovery
A total body irradiation (TBI) model is appropriate for triage and definitive dose assay in the first few days following irradiation, there is interest in understanding how partial body irradiation impacts the metabolomic signature during the early days post-exposure
The emerging field of radiation metabolomics provides a fascinating alternative to classical radiation biodosimetry approaches
Summary
There is currently an urgent, unmet need for biodosimetry tests to detect radiation exposure levels, to be deployed in the event of a large-scale nuclear incident, and to monitor injury progression and recovery. To address this and other requirements, the Radiation and Nuclear Countermeasure. The toolkit available to first responders and health professionals to respond to a radiological/nuclear incident will likely require multiple biodosimetry tests, such as (1) field-deployable methods to assess ≥2 Gy exposure in humans for triage, (2) laboratory-based, high throughput assays to determine definitive total body or partial body dose to the exposed individual [4,5], and (3) approaches to predict immediate and long-term consequences of radiation injury (Table 1). Apart from the classical cytogenetic assays (e.g., dicentric chromosome assay, micronucleus assay, and other DNA damage assessment methods), current technologies have expanded rapidly, to include proteomic, genomic, lipidomics, metabolomic, transcriptomic, and additional cytogenetic markers, such as gamma-H2AX foci [6]
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