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Comprehensive Characterization and Identification of DNA Adducts Induced by Formaldehyde with High-Resolution Mass Spectrometry-Based DNA Adductomics Approach
Mass spectrometry (MS)-based DNA adductomics has been recently developed. It is a novel tool that enables a comprehensive investigation of DNA adducts induced by the endogenous or exogenous exposures. Particularly, methods based on high-resolution mass spectrometry (HRMS) provide useful accurate mass measurement and structural information for identification of DNA adducts.
In the present study, we developed a liquid chromatography-HRMS-based DNA adductomics approach with data-dependent constant neutral loss MS3 (DD-CNL-MS3) screening mode, to broadly screen for both known and unknown DNA adducts. To test the feasibility of this method, we measured all the potential DNA adducts formed in calf thymus DNA following the formaldehyde (a human carcinogen) treatment. Our results showed that some expected DNA adducts (e.g., N6-hydroxymethyl-2'-deoxyadenosine, N6-hmdA) were detected, and a number of unexpected DNA adducts were newly formed after the formaldehyde treatment. Newly formed DNA adducts were further successfully identified with their accurate mass of precursor ion and the corresponding MSn fragment ions. The present DNA adductomics approach using LC-HRMS could be a powerful tool for comprehensively screening for the DNA adducts induced by endogenous or exogenous exposures.