Abstract
Purpose: There is a need to identify new biomarkers of radiation exposure both for use in the development of biodosimetry blood diagnostics for radiation exposure and for clinical use as markers of radiation injury. In the current study, a novel high-throughput proteomics screening approach was used to identify proteomic markers of radiation exposure in the plasma of total body irradiated mice. A subset panel of significantly altered proteins was selected to build predictive models of radiation exposure and received radiation dose useful for population screening in a future radiological or nuclear event. Methods: Female C57BL6 Mice of 8–14 weeks of age received a single total body irradiation (TBI) dose of 2, 3.5, 8 Gy or sham radiation and plasma was collected by cardiac puncture at days 1, 3, and 7 post-exposure. Plasma was then screened using the aptamer-based SOMAscan proteomic assay technology, for changes in expression of 1,310 protein analytes. A subset panel of protein biomarkers which demonstrated significant changes (p < 0.05) in expression following radiation exposure were used to build predictive models of radiation exposure and radiation dose. Results: Detectable values were obtained for all 1,310 proteins included in the SOMAscan assay. For the Control vs. Radiation model, the top predictive proteins were immunoglobulin heavy constant mu (IGHM), mitogen-activated protein kinase 14 (MAPK14), ectodysplasin A2 receptor (EDA2R) and solute carrier family 25 member 18 (SLC25A18). For the Control vs. Dose model, the top predictive proteins were cyclin dependent kinase 2/cyclin A2 (CDK2. CCNA2), E-selectin (SELE), BCL2 associated agonist of cell death (BAD) and SLC25A18. Following model validation with a training set of samples, both models tested with a new sample cohort had overall predictive accuracies of 85% and 73% for the Control vs. Radiation and Control vs. Dose models respectively. Conclusion: The SOMAscan proteomics platform is a useful screening tool to evaluate changes in biomarker expression. In our study we were able to identify a novel panel of radiation responsive proteins useful for predicting whether an animal had received a radiation exposure and to what dose they had received. Such diagnostic tools are needed for future medical management of radiation exposures.
Highlights
Mass casualty medical management of potential radiological or nuclear events primarily require diagnostics to effectively identify individuals who have received a radiation exposure
At the proteomic level several key biomarkers of radiation exposure have been established in mammalian models of radiation exposure and include Flt3 ligand (FL), a marker of hematopoietic stem cell recovery, acute phase response proteins c-reactive protein (CRP) and serum amyloid A (SAA) and other markers such as salivary alpha amylase (AMY1) and monocyte chemotactic protein 1 (MCP1) (Ossetrova et al, 2011; Sproull et al, 2017; Balog et al, 2019)
We developed a “Control vs. Dose” model to predict how great a radiation dose an individual had received which is useful for guiding subsequent medical management decisions
Summary
Mass casualty medical management of potential radiological or nuclear events primarily require diagnostics to effectively identify individuals who have received a radiation exposure. Many promising approaches are currently under development including point-of-care and high-throughput off-site approaches (Garty et al, 2016; Balog et al, 2020; Jacobs et al, 2020). These diagnostics are based on physiological biomarkers of radiation injury found primarily in the blood and include a wide array of molecules at the genomic, proteomic, metabolomic, and transcriptomic level. Some methodologies for characterizing radiation exposure utilize cytogenetic markers, lymphocyte depletion kinetics and electron paramagnetic resonance (EPR) This variety of biomarker classes represent the complex physiologic interaction of biological mechanisms involved in ionizing radiation injury (Sproull and Camphausen, 2016). At the proteomic level several key biomarkers of radiation exposure have been established in mammalian models of radiation exposure and include Flt ligand (FL), a marker of hematopoietic stem cell recovery, acute phase response proteins c-reactive protein (CRP) and serum amyloid A (SAA) and other markers such as salivary alpha amylase (AMY1) and monocyte chemotactic protein 1 (MCP1) (Ossetrova et al, 2011; Sproull et al, 2017; Balog et al, 2019)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
