Abstract
The measurement of DNA adducts, the covalent modifications of DNA upon the exposure to the environmental and dietary genotoxicants and endogenously produced electrophiles, provides molecular evidence for DNA damage. With the recent improvements in the sensitivity and scanning speed of mass spectrometry (MS) instrumentation, particularly high-resolution MS, it is now feasible to screen for the totality of DNA damage in the human genome through DNA adductomics approaches. Several MS platforms have been used in DNA adductomic analysis, each of which has its strengths and limitations. The loss of 2′-deoxyribose from the modified nucleoside upon collision-induced dissociation is the main transition feature utilized in the screening of DNA adducts. Several advanced data-dependent and data-independent scanning techniques originated from proteomics and metabolomics have been tailored for DNA adductomics. The field of DNA adductomics is an emerging technology in human exposure assessment. As the analytical technology matures and bioinformatics tools become available for analysis of the MS data, DNA adductomics can advance our understanding about the role of chemical exposures in DNA damage and disease risk.
Highlights
Humans are frequently exposed to a wide variety of environmental and dietary genotoxicants and endogenously produced electrophiles
DNA adducts formed at critical sites in tumor-related genes are believed to be the first step in chemical carcinogenesis [1]
The modified SWATH-data-independent acquisition (DIA), (H) wide-SIM/MS2, has been used to scan for multiple DNA adducts, in which both mass spectrometry (MS) and MS2 are separated into smaller windows, which improves the sensitivity of detection of precursor adducts and the aglycones
Summary
Humans are frequently exposed to a wide variety of environmental and dietary genotoxicants and endogenously produced electrophiles These reactive species can damage DNA and form covalent modifications, known as adducts. The modified SWATH-DIA, (H) wide-SIM/MS2, has been used to scan for multiple DNA adducts, in which both MS and MS2 are separated into smaller windows, which improves the sensitivity of detection of precursor adducts and the aglycones. Fragmentation (F) in one scan event, and the identification of a DNA adduct relies on the co-elution of the precursor and fragment ions. The modified SWATH-DIA, (H) wide-SIM/MS2, has been used to scan for multiple DNA adducts, in which both MS and MS2 are High-Thsreopuaghraputetd20i1n9t,o8,s1m3 aller windows, which improves the sensitivity of detection of precursor adduct5s of 25 and the aglycones.
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