BAX and DDB2 as biomarkers for acute radiation exposure with in the first week after irradiation in ex-vivo human and nonhuman primate model

Abstract

There are currently no available FDA-cleared biodosimetry tools for rapid and accurate assessment of radiation absorbed dose following a radiation/nuclear incident. The objective of this work is to support analytical testing of our ELISA-based bioassay system for biodosimetry. The prediction accuracy of the bioassay for exposure classification and dose reconstruction was determined by combining BAX and DDB2 protein expression levels and cell counts/viability in adult human and non-human primate (NHP; Rhesus macaques) leukocytes, irradiated ex vivo with 0 to 5 Gy X rays using machine learning methods. The bioassay showed a 97.92% and 96.15% accuracy in classifying the human and NHP in-vitro samples up to 48 h after exposure, respectively and an adequate correlation between reconstructed and actual dose in the human samples (R² = 0.79, RMSE = 0.80 Gy, and MAE = 0.63 Gy) and NHP (R² = 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 here show that using a combined approach of targeted protein analysis can increase bioassay sensitivity and provide a more accurate dose prediction.