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DNA 修饰:暴露组学的生物标志物?

DNA modifications: Biomarkers for the exposome?

机构信息

Oxidative Stress Group, Department of Molecular Biosciences, University of South Florida, Tampa, FL 33620, USA.

Oxidative Stress Group, Department of Molecular Biosciences, University of South Florida, Tampa, FL 33620, USA.

出版信息

Environ Toxicol Pharmacol. 2024 Jun;108:104449. doi: 10.1016/j.etap.2024.104449. Epub 2024 Apr 16.

DOI:10.1016/j.etap.2024.104449
PMID:38636743
Abstract

The concept of the exposome is the encompassing of all the environmental exposures, both exogenous and endogenous, across the life course. Many, if not all, of these exposures can result in the generation of reactive species, and/or the modulation of cellular processes, that can lead to a breadth of modifications of DNA, the nature of which may be used to infer their origin. Because of their role in cell function, such modifications have been associated with various major human diseases, including cancer, and so their assessment is crucial. Historically, most methods have been able to only measure one or a few DNA modifications at a time, limiting the information available. With the development of DNA adductomics, which aims to determine the totality of DNA modifications, a far more comprehensive picture of the DNA adduct burden can be gained. Importantly, DNA adductomics can facilitate a "top-down" investigative approach whereby patterns of adducts may be used to trace and identify the originating exposure source. This, together with other 'omic approaches, represents a major tool for unraveling the complexities of the exposome and hence allow a better a understanding of the environmental origins of disease.

摘要

暴露组学的概念是指在整个生命过程中,包含所有的环境暴露,包括外源性和内源性暴露。这些暴露中的许多(如果不是全部的话)都会导致活性物质的产生,和/或细胞过程的调节,从而导致 DNA 的广泛修饰,其性质可用于推断其来源。由于它们在细胞功能中的作用,这些修饰与各种人类重大疾病有关,包括癌症,因此对其进行评估至关重要。从历史上看,大多数方法一次只能测量一种或几种 DNA 修饰,限制了可用信息的数量。随着旨在确定 DNA 修饰总量的 DNA 加合物组学的发展,可以更全面地了解 DNA 加合物负担。重要的是,DNA 加合物组学可以促进一种“自上而下”的研究方法,通过这种方法,可以使用加合物模式来追踪和识别原始暴露源。这与其他“组学”方法一起,代表了解开暴露组学复杂性的主要工具,从而更好地理解疾病的环境起源。

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Exposomics: a review of methodologies, applications, and future directions in molecular medicine.暴露组学:分子医学中的方法、应用及未来方向综述
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