Multiple blood-proteins approach for early-response exposure assessment using an in vivo murine radiation model

PURPOSE: The aim was to evaluate the utility of multiple blood-protein biomarkers for early-response assessment of radiation exposure using a murine radiation model system. MATERIAL AND METHODS: BALB/c male mice (8-10 weeks old) were exposed to whole-body 60Co gamma-rays (10 cGy min(-1)) over a broad dose range (0-7 Gy). Blood protein biomarkers (i.e., Growth Arrest and DNA Damage Inducible Gene 45 or GADD45alpha, interleukin 6 or IL-6, and serum amyloid A or SAA) were measured by enzyme linked immunosorbent assay (ELISA) at 4, 24, 48, and 72 h after total-body irradiation (TBI). RESULTS: Time- and dose-dependent increases in the protein targets were observed. The use of multiple protein targets was evaluated using multiple linear regression analysis to provide dose-response calibration curves for dose assessment. Multivariate discriminant analysis demonstrated enhanced dose-dependent separation of irradiated animals from control as the number of biomarkers increased. CONCLUSIONS: Results from this study represent a proof-of-concept for multiple blood-proteins biodosimetry approach. It was demonstrated for the first time that protein expression profile could be developed not only to assess radiation exposure in male BALB/c mice but also to distinguish the level of radiation exposure, ranging from 1-7 Gy.