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在非人类灵长类动物中建立口腔屏蔽的半身照射模型的特性研究。

Characterization of a partial-body irradiation model with oral cavity shielding in nonhuman primates.

机构信息

CiToxLAB North America, Laval, QC, Canada.

Soligenix, Inc., Princeton, NJ, USA.

出版信息

Int J Radiat Biol. 2020 Jan;96(1):100-111. doi: 10.1080/09553002.2018.1440093. Epub 2018 Apr 3.

Abstract

Characterization of a novel partial-body irradiation (PBI) shielding strategy in nonhuman primates (NHP; rhesus macaques), aimed at protecting the oral cavity, with respect to various gastrointestinal acute radiation syndrome (GI-ARS) syndrome parameters as well as buccal ulceration development. NHPs were irradiated using a Cobalt-60 gamma source, in a single uniform dose, ranging from 9-13 Gy and delivered at 0.60-0.80 Gy min. Animals were either partially shielded via oral cavity shielding (PBI) or underwent total-body irradiation (TBI). Clinical manifestations of GI-ARS, and also radiation-induced hematology and clinical chemistry changes, following PBI were comparable to the PBI NHP GI-ARS model utilizing shielding of the distal pelvic limbs and were significantly milder than TBI at similar radiation doses. Nadir citrulline levels were comparable between PBI and TBI but signs of recovery appeared earlier in PBI-treated animals. The PBI model prevented oral mucositis, whereas the TBI model presented buccal ulcerations at all tested radiation dose levels. Taken together, these results suggest that the PBI model is a suitable alternative to traditional PBI. For GI-ARS investigations requiring orally administered medical countermeasures, PBI confers added value due to the prevention of oral mucositis over traditional PBI.

摘要

一种新型的非人类灵长类动物(NHP;恒河猴)半身局部照射(PBI)屏蔽策略的特点,旨在保护口腔,针对各种胃肠道急性辐射综合征(GI-ARS)综合征参数以及口腔溃疡发展。使用钴-60 伽马源对 NHP 进行单次均匀剂量照射,剂量范围为 9-13Gy,剂量率为 0.60-0.80Gy min。动物通过口腔屏蔽(PBI)进行部分屏蔽或进行全身照射(TBI)。与利用远侧骨盆肢体屏蔽的 PBI NHP GI-ARS 模型相比,PBI 后的 GI-ARS 临床表现以及辐射诱导的血液学和临床化学变化相当,并且比相似剂量的 TBI 明显更轻。PBI 和 TBI 之间的柠檬酸水平最低值相当,但 PBI 治疗动物的恢复迹象更早出现。PBI 模型可预防口腔粘膜炎,而 TBI 模型在所有测试的辐射剂量水平下均出现口腔溃疡。总之,这些结果表明 PBI 模型是传统 PBI 的一种合适替代方法。对于需要口服给予医疗对策的 GI-ARS 研究,由于 PBI 可预防口腔粘膜炎,因此比传统 PBI 具有附加价值。

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