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After a radiological incident, there is an urgent need for fast and reliable bioassays to identify radiation-exposed individuals within the first week post exposure. This study aimed to identify candidate radiation-responsive protein biomarkers in human lymphocytes  in vivo  using humanized NOD scid gamma (Hu-NSG) mouse model. Three days after X-irradiation (0–2 Gy, 88 cGy/min), human CD45+ lymphocytes were collected from the Hu-NSG mouse spleen and quantitative changes in the proteome of the human lymphocytes were analysed by mass spectrometry. Forty-six proteins were differentially expressed in response to radiation exposure. FDXR, BAX, DDB2 and ACTN1 proteins were shown to have dose-dependent response with a fold change greater than 2. When these proteins were used to estimate radiation dose by linear regression, the combination of FDXR, ACTN1 and DDB2 showed the lowest mean absolute errors (≤0.13 Gy) and highest coefficients of determination (R 2  = 0.96). Biomarker validation studies were performed in human lymphocytes 3 days after irradiation  in vivo  and  in vitro . In conclusion, this is the first study to identify radiation-induced human protein signatures  in vivo  using the humanized mouse model and develop a protein panel which could be used for the rapid assessment of absorbed dose 3 days after radiation exposure.

Candidate protein markers for radiation biodosimetry in the hematopoietically humanized mouse model