Discover and identify unknown alkylation DNA adducts induced by sulfonates using prediction driven -MRM-profiling strategy.

Yu Tang, Xiong Chen, Dongmei Wang, Ruiping Zhang, Jinlan Zhang

Talanta 2021 Jan 15

filter terms:

Alkylated DNA adducts are the most important and common form of DNA damage at the molecular level. In addition to known alkylated DNA adducts, many unknown DNA adducts remain to be discovered. A prediction-driven MRM profiling MS strategy has been established for the rapid discovery of unknown DNA adducts induced by sulfonates. The innovative aspects and core of this strategy are the construction of the prediction MRM list, which includes 36 possible precursor ion and characteristic product ion transitions of DNA adducts based on MS fragmentation patterns, and then unknown DNA adducts 7-propyl guanine and 7-butyl guanine were discovered based on the diagnostic MRM signals of the DNA samples, and subsequently confirmed using high-resolution MS data and synthetic standards for the first time. Furthermore, DNA adducts, including newly found adducts in a human cell model and rat tissues after nitrosamine and sulfonate exposure, were unambiguously investigated by a UHPLC-MS/MS method. As a result, different alkyl methanesulfonates, including methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), PMS and BMS, all lead to the formation of 7MeG in addition to their own specific alkylation DNA adducts. The ester group of the sulfonate determines the specific types of DNA adducts produced, and the sulfonate might undergo transesterification with the methyl donors that commonly exist in eukaryotic organisms such as SAM, resulting in the formation of MMS, which induce the generation of methyl DNA adducts after EMS, PMS and BMS exposure. Furthermore, similar DNA adduct profiles were presented in both human cells and rat tissues. This approach could be useful in the future for probing unknown DNA adducts and simultaneously profiling both known and unknown DNA adducts in both in vitro to in vivo settings to evaluate potential genotoxicities and cancer risks to populations exposed to genotoxins. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Yu Tang, Xiong Chen, Dongmei Wang, Ruiping Zhang, Jinlan Zhang. Discover and identify unknown alkylation DNA adducts induced by sulfonates using prediction driven -MRM-profiling strategy. Talanta. 2021 Jan 15;222:121500