Assessment of host responses to ionizing radiation. Mus musculus

The aim of this study was to analyze the host responses to ionizing radiation by nuclear factor-κB (NF-κB) bioluminescence imaging-guided transcriptomic tool. Transgenic mice, carrying the NF-κB-driven luciferase gene, were exposed to a single dose of 8.5 Gy total-body irradiation. In vivo imaging showed that a maximal NF-κB-dependent bioluminescent intensity was observed at 3 h after irradiation and ex vivo imaging showed that liver, intestine, and brain displayed strong NF-κB activations. Microarray analysis of these organs showed that irradiation altered gene expression signatures in an organ-specific manner. Pathway analysis showed that pathways associated with metabolism and immune system were altered primarily in liver and intestine. the upregulation of fatty acid binding protein 4, serum amyloid A2, and serum amyloid A3, which are participated in both inflammation and lipid metabolism, suggesting that irradiation might affect the cross pathways of metabolism and inflammation. Moreover, The upregulation of chemokine (CC-motif) ligand 5, chemokine (CC-motif) ligand 20, and Jagged 1 genes suggested that these genes might contribute to the radiation enteropathy. Overall design: Male transgenic mice (6 to 8 weeks old) were exposed to a single dose of whole-body X-rays generated at 6 MV (Clinac® 21EX medical linear accelerator, Varian, Palo Alto, CA, USA) and at a dose rate of 4 Gy/min. Mice were imaged at 0 h, 1 h, 3 h, 9 h, 24 h, 48 h, or 72 h, or on 7 d or 14 d after irradiation with 8.5 Gy. RNAs were extracted at 3 h after irradiation.