Menon Smrithi S, Uppal Medha, Randhawa Subeena, Cheema Mehar S, Aghdam Nima, Usala Rachel L, Ghosh Sanchita P, Cheema Amrita K, Dritschilo Anatoly
Department of Oncology, Georgetown University Medical Center , Washington, DC , USA.
Department of Radiation Medicine, Georgetown University Medical Center , Washington, DC , USA.
Front Oncol. 2016 Feb 2;6:20. doi: 10.3389/fonc.2016.00020. eCollection 2016.
Human exposure to ionizing radiation (IR) disrupts normal metabolic processes in cells and organs by inducing complex biological responses that interfere with gene and protein expression. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as organ- and tissue-specific biomarkers for personnel exposed to radiation, particularly, weeks or months after exposure. Analysis of metabolites generated in known stress-responsive pathways by molecular profiling helps to predict the physiological status of an individual in response to environmental or genetic perturbations. Thus, a multi-metabolite profile obtained from a high-resolution mass spectrometry-based metabolomics platform offers potential for identification of robust biomarkers to predict radiation toxicity of organs and tissues resulting from exposures to therapeutic or non-therapeutic IR. Here, we review the status of radiation metabolomics and explore applications as a standalone technology, as well as its integration in systems biology, to facilitate a better understanding of the molecular basis of radiation response. Finally, we draw attention to the identification of specific pathways that can be targeted for the development of therapeutics to alleviate or mitigate harmful effects of radiation exposure.
人类暴露于电离辐射(IR)会通过引发复杂的生物反应来干扰细胞和器官中的正常代谢过程,这些生物反应会干扰基因和蛋白质表达。传统的剂量测定、前驱症状监测和外周淋巴细胞计数作为暴露于辐射人员的器官和组织特异性生物标志物,其价值有限,尤其是在暴露数周或数月之后。通过分子谱分析已知应激反应途径中产生的代谢物,有助于预测个体对环境或基因扰动的生理状态。因此,从基于高分辨率质谱的代谢组学平台获得的多代谢物谱,为识别强大的生物标志物以预测治疗性或非治疗性IR暴露导致的器官和组织辐射毒性提供了潜力。在此,我们综述辐射代谢组学的现状,并探讨其作为一项独立技术的应用,以及它在系统生物学中的整合,以促进对辐射反应分子基础的更好理解。最后,我们提请注意识别特定途径,这些途径可作为开发治疗方法的靶点,以减轻或缓解辐射暴露的有害影响。