Open AccessComprehensive Analysis of DNA Adducts Using Data-Independent wSIM/MS2 Acquisition and wSIM-City
Author(s) -
Scott J. Walmsley,
Jingshu Guo,
Paari Murugan,
Christopher J. Weight,
Jinhua Wang,
Peter W. Villalta,
Robert J. Turesky
Publication year - 2021
Publication title -
analytical chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.117
H-Index - 332
eISSN - 1520-6882
pISSN - 0003-2700
DOI - 10.1021/acs.analchem.1c00362
Subject(s) - chemistry , dna , adduct , deoxyribose , electrophile , protonation , fragmentation (computing) , combinatorial chemistry , biochemistry , organic chemistry , ion , computer science , operating system , catalysis
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.