Search

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. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • Evaluation of the exposome, across the lifecourse, is a significant challenge. • DNA adductomics aims to determine the totality of adducts in the genome. • Cellular DNA adductomics invariably requires sampling tissue e.g., blood. • Urinary DNA adductomics non-invasively reflects the body burden totality of adducts. [ABSTRACT FROM AUTHOR]