Comprehensive Analysis of DNA Adducts Using Data-Independent wSIM/MS² Acquisition and wSIM-City.

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 MS² 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 MS² fragmentation. This untargeted approach can detect DNA adducts at trace levels as low as 1.5 adducts per 10⁹ nucleotides. This level of sensitivity is sufficient for comprehensive analysis and characterization of DNA modifications in human specimens.

SUBMITTER: Walmsley SJ 

PROVIDER: S-EPMC8675643 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature