Journal Article

BAX and DDB2 as biomarkers for acute radiation exposure in the human blood ex vivo and non-human primate models

Kanagaraj, Karthik, Phillippi, Michelle A., Schaaf, George, Shuryak, Igor, Kleiman, Norman J., Turner, Helen C., Cline, J. Mark, Ober, Elizabeth H., Olson, John

2024

Overview

There are currently no available FDA-cleared biodosimetry tools for rapid and accurate assessment of absorbed radiation dose following a radiation/nuclear incident. Previously we developed a protein biomarker-based FAST-DOSE bioassay system for biodosimetry. The aim of this study was to integrate an ELISA platform with two high-performing FAST-DOSE biomarkers, BAX and DDB2, and to construct machine learning models that employ a multiparametric biomarker strategy for enhancing the accuracy of exposure classification and radiation dose prediction. The bioassay showed 97.92% and 96% accuracy in classifying samples in human and non-human primate (NHP) blood samples exposed ex vivo to 0–5 Gy X-rays, respectively up to 48 h after exposure, and an adequate correlation between reconstructed and actual dose in the human samples (R 2  = 0.79, RMSE = 0.80 Gy, and MAE = 0.63 Gy) and NHP (R 2  = 0.80, RMSE = 0.78 Gy, and MAE = 0.61 Gy). Biomarker measurements in vivo from four NHPs exposed to a single 2.5 Gy total body dose showed a persistent upregulation in blood samples collected on days 2 and 5 after irradiation. The data indicates that using a combined approach of targeted proteins can increase bioassay sensitivity and provide a more accurate dose prediction.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 692/308/53/2423 / 692/53/2423 / Animals / bcl-2-Associated X Protein - blood / bcl-2-Associated X Protein - metabolism / Bioassays / Biodosimetry / Biomarkers / Biomarkers - blood / Blood / DNA-Binding Proteins - blood / ELISA / Female / Humanities and Social Sciences / Humans / Intracellular proteins / Irradiation / Macaca mulatta / Machine Learning / Male / multidisciplinary / Protein biomarkers / Radiation / Radiation Dosage / Radiation Exposure - adverse effects / Radiometry - methods / Science / Science (multidisciplinary)