Oxidative Stress Group, Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA; Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
Oxidative Stress Group, Department of Environmental Health Sciences, Florida International University, Miami, FL 33199, USA; Department of Public Health, Chung Shan Medical University, Taichung 402, Taiwan.
Environ Int. 2018 Dec;121(Pt 2):1033-1038. doi: 10.1016/j.envint.2018.10.041. Epub 2018 Nov 2.
The exposome is a concept that encompasses the totality of internal and external environmental exposures, from conception onwards. Evaluation of the exposome, across the lifecourse represents a significant challenge, e.g., methods/technology may simply not exist to comprehensively assess all exposures, or they may not be applicable to human populations, or may have insufficient sensitivity. Cellular DNA adductomics aims to determine the totality of DNA adducts in the cellular genome. However, application to human populations requires the necessarily invasive sampling of tissue, to obtain sufficient DNA for sensitive analysis, which can represent a logistical and IRB challenge, particularly when investigating vulnerable populations. To circumvent this, we recently applied DNA adductomics to urine, detecting a range of expected and unexpected 2'-deoxyribonucleoside DNA adducts. However, base excision repair, the main DNA repair pathway for non-bulky DNA adducts, and processes such as spontaneous depurination, generate nucleobase adducts. Herein we propose a strategy to simultaneously assess 2'-deoxyribonucleoside and nucleobase adducts, using a widely used mass spectrometic platform (i.e., triple quadrupole tandem mass spectrometry). This will provide a much needed DNA adductomic approach for non-invasively, biomonitoring environmental exposures, through assessing the totality of DNA adducts; contributing to the evaluation of the exposome, across the life-course.
暴露组学是一个概念,涵盖了从受孕开始的所有内部和外部环境暴露。评估整个生命过程中的暴露组学是一个重大挑战,例如,可能没有方法/技术可以全面评估所有暴露,或者它们可能不适用于人类群体,或者可能敏感性不足。细胞 DNA 加合物组学旨在确定细胞基因组中 DNA 加合物的总和。然而,将其应用于人类群体需要对组织进行必要的侵入性采样,以获得足够的 DNA 进行敏感分析,这可能会带来后勤和 IRB 方面的挑战,特别是在研究弱势群体时。为了避免这种情况,我们最近将 DNA 加合物组学应用于尿液,检测到一系列预期和意外的 2'-脱氧核苷 DNA 加合物。然而,非大体积 DNA 加合物的主要 DNA 修复途径碱基切除修复以及自发脱嘌呤等过程会产生核碱基加合物。在此,我们提出了一种使用广泛使用的质谱平台(即三重四极杆串联质谱)同时评估 2'-脱氧核苷和核碱基加合物的策略。这将为通过评估 DNA 加合物的总和,提供一种急需的非侵入性生物监测环境暴露的 DNA 加合物组学方法;为评估整个生命过程中的暴露组学做出贡献。