Spleen Transcriptome of Nonhuman Primates Exposed to High Doses of Total- or Partial-Body Radiation: Comparisons with Jejunum and Lung

Total-body irradiation (TBI) and partial-body irradiation (PBI) after a radiological or nuclear event result in acute radiation syndrome. Such radiation-induced injuries require immediate diagnosis and treatment. New strategies are required for radiation biodosimetry, along with the advancement of mitigation measures. Understanding gene expression alterations in irradiated cells pretreated with medical countermeasure (MCM) reveals the complex cellular responses to radiation and the radioprotective efficacy of MCM. In this study, we analyzed transcriptomic responses in irradiated nonhuman primate (NHP) tissues pretreated with gamma-tocotrienol (GT3) to evaluate GT3 efficacy and irradiation's tissue impact. Transcriptomic responses are evaluated for gender differences. Additionally, we compared spleen responses with those of lung and jejunum. Our study demonstrates that the spleen is vulnerable to radiation-induced gene expression changes compared to the lung and jejunum. Both TBI and PBI significantly impacted pathways related to cell proliferation, immune function, pathogen response, and disease processes. We identified radiation-induced alterations in p53 signaling and its target gene expression across spleen, lung, and jejunum, with p53 activation attenuated in the spleen than in the other organs. No significant sex-based differences were observed in irradiated NHPs. In addition, a lower dose of GT3 pretreatment was ineffective in protecting against a supralethal 12 Gy radiation dose in either model. Overall, these findings provide important insights into the molecular changes induced by GT3 treatment and radiation, highlighting opportunities to identify biomarkers of radiation injury and to develop MCMs.