| Summary |
Radiation biodosimetry based on transcriptomic analysis of peripheral blood is a valuable tool to detect radiation exposure after a radiological/nuclear event and obtain useful biological information that could predict tissue and organismal injury. However, confounding factors, including inflammation, can potentially obscure the predictive power of the method. The Gadd45 (growth arrest and DNA damage-inducible genes) family is composed of three members, Gadd45a, Gadd45b, and Gadd45g, that play important roles in cell growth control, differentiation, DNA repair, and apoptosis. Gadd45b and Gadd45g are important for inflammatory responses as well as mediating signals of the innate immune system, whereas Gadd45a is a negative regulator of activation-induced T cell proliferation. T cells from Gadd45a null mice are hyper-responsive to activating stimuli due to spontaneously increased p38MAPK activity. Importantly, Gadd45a-deficient mice develop an autoimmune disease, similar to human systemic lupus erythematosus, characterized by severe hematological disorders, kidney disease, and premature death. The goal of this study was to elucidate how pre-existing inflammatory condition in mice can affect radiation biodosimetry. We exposed wild-type and Gadd45a knockout C57BL/6J mice to 7 Gy x-rays and 24 h later we isolated whole blood and performed genome microarray and gene ontology analysis.
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