Comprehensive Analysis of DNA Adducts Using Data-Independent wSIM/MS 2 Acquisition and wSIM-City
Year: 2021
Type: article
Abstract: A novel software has been created to comprehensively characterize covalent modifications of DNA through mass spectral analysis of enzymatically hydrolyzed DNA using the neutral loss of 2′-deoxyribose, a nearly universal MS 2 fragmentation process of protonated 2′-deoxyribonucleosides. These covalent modifications termed DNA adducts form through xenobiotic exposures or by reaction with endogenous electrophiles and can induce mutations during cell division and initiate carcinogenesis. DNA adducts are typically present at trace levels in the human genome, requiring a very sensitive and comprehensive data acquisition and analysis method. Our software, wSIM-City, was created to process mass spectral data acquired by a wide selected ion monitoring (wSIM) with gas-phase fractionation and coupled to wide MS 2 fragmentation. This untargeted approach can detect DNA adducts at trace levels as low as 1.5 adducts per 10 9 nucleotides. This level of sensitivity is sufficient for comprehensive analysis and characterization of DNA modifications in human specimens.
Source: Analytical Chemistry
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: New biomonitoring methodologies to measure DNA adducts in human tissues, University of Minnesota Clinical and Translational Science Institute (UMN CTSI), Minnesota HHEAR Targeted Analysis Laboratory, G2915001239, Kidney DNA Adductomics, DNA adductomics of the urinary system, Development of a DNA Adductome Database, Chemical markers of heterocyclic aromatic amines for human biomonitoring, Mass Spectrometric Analytical Collaborations with Members of the Carcinogenesis and Chemoprevention Program of the University of Minnesota Masonic Cancer Center, Cancer Center Support Grant
OpenAlex ID: W3154622338