Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques.
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Duke Scholars
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- Whole-Body Irradiation
- T-Lymphocytes
- Radiation Injuries, Experimental
- RNA, Messenger
- Ovariectomy
- Oncology & Carcinogenesis
- Macrophages
- Macaca fascicularis
- Lymphoid Tissue
- Gene Expression Profiling
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Whole-Body Irradiation
- T-Lymphocytes
- Radiation Injuries, Experimental
- RNA, Messenger
- Ovariectomy
- Oncology & Carcinogenesis
- Macrophages
- Macaca fascicularis
- Lymphoid Tissue
- Gene Expression Profiling