Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20001, USA.
Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20001, USA.
Int J Mol Sci. 2019 Jul 9;20(13):3360. doi: 10.3390/ijms20133360.
Exposure to ionizing radiation induces a complex cascade of systemic and tissue-specific responses that lead to functional impairment over time in the surviving population. However, due to the lack of predictive biomarkers of tissue injury, current methods for the management of survivors of radiation exposure episodes involve monitoring of individuals over time for the development of adverse clinical symptoms and death. Herein, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that were exposed to a single dose of 7.2 Gy whole-body Co γ-radiation that either survived or succumbed to radiation toxicities over a 60-day period. This study involved the delineation of the radiation effects in the liver, kidney, jejunum, heart, lung, and spleen. We found robust metabolic changes in the kidney and liver and modest changes in other tissue types at the 60-day time point in a cohort of NHPs. Remarkably, we found significant elevation of long-chain acylcarnitines in animals that were exposed to radiation across multiple tissue types underscoring the role of this class of metabolites as a generic indicator of radiation-induced normal tissue injury. These studies underscore the utility of a metabolomics approach for delineating anticipatory biomarkers of exposure to ionizing radiation.
暴露于电离辐射会引起一系列复杂的全身性和组织特异性反应，随着时间的推移，幸存人群的功能会逐渐受损。然而，由于缺乏组织损伤的预测性生物标志物，目前对辐射暴露事件幸存者的管理方法涉及随着时间的推移监测个体不良临床症状的发展和死亡。在此，我们报告了在 60 天内接受单次 7.2Gy 全身 Co γ 射线照射的非人类灵长类动物（NHP）的多个组织中代谢组学和脂质组学图谱的变化，这些 NHP 要么幸存，要么死于辐射毒性。本研究涉及肝脏、肾脏、空肠、心脏、肺和脾脏中辐射效应的描述。我们发现，在接受辐射的 NHP 队列中，在 60 天时间点，肾脏和肝脏的代谢变化明显，而其他组织类型的变化适度。值得注意的是，我们发现暴露于辐射的多种组织类型中的长链酰基辅酶 A 显著升高，这强调了这类代谢物作为辐射诱导的正常组织损伤的通用指标的作用。这些研究强调了代谢组学方法在描绘电离辐射暴露的预期生物标志物方面的效用。
