Golla Srujana, Golla Jaya Prakash, Krausz Kristopher W, Manna Soumen K, Simillion Cedric, Beyoğlu Diren, Idle Jeffrey R, Gonzalez Frank J
a Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
b Interfaculty Bioinformatics Unit and SIB Swiss Institute of Bioinformatics, University of Bern, Baltzerstrasse 6, 3012 Bern, Switzerland.
Radiat Res. 2017 May;187(5):612-629. doi: 10.1667/RR14592.1. Epub 2017 Mar 9.
Diagnostic markers are needed for accidental or deliberate radiation exposure that could cause acute and chronic radiation toxicity. Biomarkers of temporal, dose-dependent, aging-attenuated and multiple radiation exposures have been previously described by others. However, the physiological origin and biochemical networks that generate these biomarkers and their association at the molecular level have yet to be explored. Hence, the discovery and identification of total-body-irradiation-induced tissue specific biomarkers remains an enormous challenge within radiation biodosimetry research. To determine the tissue level response of total-body exposure (6 Gy), metabolomics analysis was carried out on radiosensitive tissues bone marrow, ileum, liver, muscle and lung as well as serum and on urine within 12 h postirradiation. Differences in the metabolic signatures between the sham and gamma-irradiated groups were analyzed by hydrophilic interaction liquid chromatography (HILIC)-based ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS). A panel of 67 biomarkers identified in radiosensitive tissues and biofluids (serum and urine) at a 6 Gy dose. Among the identified biomarkers, 3-methylglutarylcarnitine (3-MGC) was found to be a novel metabolite in liver, serum and urine that could potentially be an early radiation response marker. The degree of metabolic changes among different tissues showed perturbations in pathways including DNA methylation, energy, nucleic acid, amino acid, glutathione and bile acid metabolism. These results highlight metabolomics as a potential novel approach to understand functional alterations in the metabolome that could be adapted for use in the rapid assessment of radiation exposure and triage protocols in the case of nuclear incidents.
对于可能导致急性和慢性辐射毒性的意外或故意辐射暴露，需要诊断标志物。其他人之前已经描述了与时间、剂量依赖性、衰老减弱和多次辐射暴露相关的生物标志物。然而，产生这些生物标志物的生理起源和生化网络及其在分子水平上的关联尚未得到探索。因此，在辐射生物剂量学研究中，发现和鉴定全身照射诱导的组织特异性生物标志物仍然是一个巨大的挑战。为了确定全身暴露（6 Gy）后的组织水平反应，在辐射后12小时内对辐射敏感组织骨髓、回肠、肝脏、肌肉和肺以及血清和尿液进行了代谢组学分析。通过基于亲水相互作用液相色谱（HILIC）的超高效液相色谱-电喷雾电离-四极杆飞行时间质谱（UPLC-ESI-QTOFMS）分析假照射组和γ射线照射组之间代谢特征的差异。在6 Gy剂量下，在辐射敏感组织和生物流体（血清和尿液）中鉴定出一组67种生物标志物。在鉴定出的生物标志物中，发现3-甲基戊二酰肉碱（3-MGC）是肝脏、血清和尿液中的一种新型代谢物，可能是早期辐射反应标志物。不同组织之间代谢变化的程度显示出包括DNA甲基化、能量、核酸、氨基酸、谷胱甘肽和胆汁酸代谢在内的途径受到干扰。这些结果突出了代谢组学作为一种潜在的新方法，可用于理解代谢组中的功能改变，适用于在核事故情况下快速评估辐射暴露和分类方案。
