Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques. (June 2015)

• Record Type: Journal Article
• Authors: DeBo, Ryne J.; Register, Thomas C.; Caudell, David L.; Sempowski, Gregory D.; Dugan, Gregory; Gray, Shauna; Owzar, Kouros; Jiang, Chen; Bourland, J. Daniel; Chao, Nelson J.; Cline, J. Mark
• Is Part Of: International journal of radiation biology. Volume 91:Number 6(2015:Jun.)
• Page Start: 510
• Page End: 518
• Publication Date: 2015-06
• Subjects: Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.3109/09553002.2015.1028597
• Languages: English
• ISSNs: 0955-3002

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: The threat of radiation exposure requires a mechanistic understanding of radiation-induced immune injury and recovery. The study objective was to evaluate responses to ionizing radiation in ovariectomized (surgically post-menopausal) female cynomolgus macaques.</p> <p> <italic>Materials and methods</italic>: Animals received a single total-body irradiation (TBI) exposure at doses of 0, 2 or 5 Gy with scheduled necropsies at 5 days, 8 weeks and 24 weeks post-exposure. Blood and lymphoid tissues were evaluated for morphologic, cellular, and molecular responses.</p> <p> <italic>Results</italic>: Irradiated animals developed symptoms of acute hematopoietic syndrome, and reductions in thymus weight, thymopoiesis, and bone marrow cellularity. Acute, transient increases in plasma monocyte chemoattractant protein 1 (MCP‐1) were observed in 5 Gy animals along with dose-dependent alterations in messenger ribonucleic acid (mRNA) signatures in thymus, spleen, and lymph node. Expression of T cell markers was lower in thymus and spleen, while expression of macrophage marker CD68 (cluster of differentiation 68) was relatively elevated in lymphoid tissues from irradiated animals.</p> <p> <italic>Conclusions</italic>: Ovariectomized female macaques exposed to moderate doses of radiation experienced increased morbidity, including acute, dose-dependent alterations in systemic and tissue-specific biomarkers, and increased macrophage/T cell ratios. The effects on mortality exceeded expectations based on previous studies in males, warranting further investigation.</p> </abstract>