Exposure to total- and partial-body irradiation following a nuclear or radiological incident result in the potentially lethal acute radiation syndromes of the gastrointestinal and hematopoietic systems in a dose- and time-dependent manner. Radiation-induced damage to the gastrointestinal tract is observed within days to weeks post-irradiation. Our objective in this study was to evaluate plasma biomarker utility for the gastrointestinal acute radiation syndrome in non-human primates after partial body irradiation with minimal bone marrow sparing through correlation with tissue and histological analyses. Plasma and jejunum samples from non-human primates exposed to partial body irradiation of 12 Gy with bone marrow sparing of 2.5% were evaluated at various time points from day 0 to day 21 as part of a natural history study. Additionally, longitudinal plasma samples from non-human primates exposed to 10 Gy partial body irradiation with 2.5% bone marrow sparing were evaluated at timepoints out to 180 d post-irradiation. Plasma and jejunum metabolites were quantified via liquid chromatography-tandem mass spectrometry and histological analysis consisted of corrected crypt number, an established metric to assess radiation-induced gastrointestinal damage. A positive correlation of metabolite levels in jejunum and plasma was observed for citrulline, serotonin, acylcarnitine, and multiple species of phosphatidylcholines. Citrulline levels also correlated with injury and regeneration of crypts in the small intestine. These results expand the characterization of the natural history of gastrointestinal acute radiation syndrome in non-human primates exposed to partial body irradiation with minimal bone marrow sparing and also provide additional data toward the correlation of citrulline with histological endpoints.

中文翻译：

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通过与组织和组织学分析的相关性，评估血浆生物标志物在非人类灵长类动物胃肠道急性放射综合征中的效用，并通过最小限度的骨髓保留进行局部照射。

在核或放射事件后暴露于全身和部分身体照射会以剂量和时间依赖性方式导致胃肠道和造血系统潜在致命的急性辐射综合征。在辐射后数日至数周内观察到辐射引起的胃肠道损伤。我们在本研究中的目的是通过与组织和组织学分析的相关性，评估非人类灵长类动物在部分身体照射后对胃肠道急性放射综合征的血浆生物标志物效用，同时保留最少的骨髓。作为自然史研究的一部分，在从第 0 天到第 21 天的不同时间点评估了来自非人类灵长类动物的血浆和空肠样本，该样本暴露于 12 Gy 的部分身体辐射，骨髓保留率为 2.5%。此外，在照射后 180 天的时间点评估了来自暴露于 10 Gy 部分身体照射并保留 2.5% 骨髓的非人类灵长类动物的纵向血浆样本。通过液相色谱-串联质谱法对血浆和空肠代谢物进行量化，组织学分析包括校正的隐窝数，这是一种评估辐射引起的胃肠道损伤的既定指标。观察到空肠和血浆中瓜氨酸、血清素、酰基肉碱和多种磷脂酰胆碱的代谢物水平呈正相关。瓜氨酸水平也与小肠隐窝的损伤和再生有关。