SRI International, Menlo Park, CA, USA.
Int J Radiat Biol. 2023;99(7):1080-1095. doi: 10.1080/09553002.2023.2188937. Epub 2023 Mar 24.
To describe the dose response relationship and natural history of radiation injury in the Wistar rat and its suitability for use in medical countermeasures (MCM) testing.
MATERIALS & METHODS: In two separate studies, male and female rats were exposed to partial body irradiation (PBI) with 5% bone marrow sparing. Animals were X-ray irradiated from 7 to 12 Gy at 7-10 weeks of age. Acute radiation syndrome (ARS) survival at 30 days and delayed effects of acute radiation exposure (DEARE) survival at 182 days were assessed. Radiation effects were determined by clinical observations, body weights, hematology, clinical chemistry, magnetic resonance imaging of lung, whole-body plethysmography, and histopathology.
Rats developed canonical ARS responses of hematopoietic atrophy and gastrointestinal injury resulting in mortality at doses ≥8Gy in males and ≥8.5 Gy in females. DEARE mortality occurred at doses ≥8Gy for both sexes. Findings indicate lung, kidney, and/or liver injury, and persistent hematological dysregulation, revealing multi-organ injury as a DEARE.
The Wistar rat PBI model is suitable for testing MCMs against hematopoietic and gastrointestinal ARS. DEARE multi-organ injury occurred in both sexes irradiated with 8-9Gy, also suggesting suitability for polypharmacy studies addressing the combination of ARS and DEARE injury.
描述 Wistar 大鼠的辐射损伤剂量反应关系和自然病史，以及其在医疗对策 (MCM) 测试中的适用性。
在两项独立的研究中，雄性和雌性大鼠接受 5%骨髓保护的全身局部照射 (PBI)。动物在 7-10 周龄时接受 7-12Gy 的 X 射线照射。在第 30 天评估急性辐射综合征 (ARS) 存活率，在第 182 天评估急性辐射暴露的延迟效应 (DEARE) 存活率。通过临床观察、体重、血液学、临床化学、肺磁共振成像、全身 plethysmography 和组织病理学来确定辐射效应。
雄性大鼠在 8Gy 及以上剂量、雌性大鼠在 8.5Gy 及以上剂量下出现典型的 ARS 反应，包括造血组织萎缩和胃肠道损伤，导致死亡。两性大鼠在 8Gy 及以上剂量下均出现 DEARE 死亡。结果表明，肺、肾和/或肝损伤以及持续的血液学失调，揭示了多器官损伤作为 DEARE。
Wistar 大鼠全身局部照射模型适用于测试针对造血和胃肠道 ARS 的 MCM。两性大鼠在接受 8-9Gy 照射后均发生 DEARE 多器官损伤，这也表明该模型适用于研究 ARS 和 DEARE 损伤联合的多药治疗。
