Lead, Genotoxic Food Contaminants Research Group, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany,
Adv Exp Med Biol. 2014;806:383-97. doi: 10.1007/978-3-319-06068-2_18.
The formation of DNA adducts is considered essential for tumor initiation. Quantification of DNA adducts may be achieved by various techniques of which LC-MS/MS-based multiple reaction monitoring has become the most prominent in the past decade. Adducts of single nucleosides are analyzed following enzymatic break-down of a DNA sample following adduct enrichment usually by solid-phase extraction. LC-MS/MS quantification is carried out using stable isotope-labeled internal reference substances. An upcoming challenge is the use of DNA adducts as biomarkers either for internal exposure to electrophilic genotoxins or for the approximation of cancer risk. Here we review recent studies in which DNA adducts were quantified by LC-MS/MS in DNA samples from human matrices. We outline a possible way for future research to aim at the development of an "adductome" approach for the characterization of DNA adduct spectra in human tissues. The DNA adduct spectrum reflects the inner exposure of an individual's tissue to electrophilic metabolites and, therefore, should replace the conventional and inaccurate external exposure in epidemiological studies in the future.
DNA 加合物的形成被认为是肿瘤发生的必要条件。DNA 加合物的定量可通过多种技术来实现，其中基于 LC-MS/MS 的多重反应监测在过去十年中变得最为突出。加合物的单核苷酸在 DNA 样品的酶解后进行分析，通常通过固相萃取进行加合物富集。LC-MS/MS 定量采用稳定同位素标记的内标物质进行。即将面临的挑战是将 DNA 加合物用作生物标志物，用于评估内源性亲电遗传毒素暴露或癌症风险。在这里，我们综述了最近通过 LC-MS/MS 在人类基质的 DNA 样本中定量 DNA 加合物的研究。我们概述了未来研究的可能方向，旨在开发一种“加合物组学”方法，用于描述人类组织中的 DNA 加合物谱。DNA 加合物谱反映了个体组织对亲电代谢物的内部暴露，因此，在未来的流行病学研究中，它应该取代传统的、不准确的外部暴露。
