Murine partial-body radiation exposure model for biodosimetry studies - Preliminary report

The objective of the present study was to establish a murine partial-body radiation exposure model for studies supporting the identification and validation of novel biological dosimetry diagnostic assays. A lead shielding - Plexiglas irradiation apparatus with cutouts to permit irradiation of single-mouse-holder constrained CD2F1 male mice to total-body (3/3), mid- and lower-body (2/3), mid-body only (1/3), and 100% lead shielding sham-treated (0 Gy) controls (0/3) with a 250-kVp X-ray source (dose: 6 Gy, dose rate: 0.50 Gy min-1) was used. Doses and dose uniformity were measured using alanine - electron paramagnetic resonance (EPR) and ionization chambers. Dosimetry mapping results showed ∼2 and ∼12% non-uniformity in the radiation fields for the two smaller (1/3, 2/3) and one larger (3/3) fields, respectively. Hematology results showed no marked differences in neutrophil and platelet counts 1 and 2 days (d) after irradiation. The lymphocyte counts, as expected, demonstrate a progressive decline below baseline levels 1 and 2 d after irradiation with increasing fraction of the body exposed, while the neutrophil to lymphocyte ratios show the inverse effect, with a progressive increase with the fraction of body exposed. The bone marrow biomarker, Flt3 ligand, demonstrated a progressive increase in values with increasing fraction of the body exposed; the 2 d response was enhanced compared to 1 d. The radioresponse 1 d after irradiation for the acute phase reactant protein biomarker, serum amyloid A (SAA) that is synthesized by the liver, was significantly influenced depending on whether the mouse head was in the radiation field. Use of multiple biomarkers based on hematology and proteomic targets provide an enhancement in early-phase partial-body radiation exposure assessment.