High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts

• An UHPLC-HRMS/MS method using Quadrupole-Orbitrap technology was developed for the detection of diet-related DNA adducts.
• A diet-related DNA adduct database was constructed.
• The method was validated and both the method and database were applied in vitro and in vivo.
• Targeted and untargeted diet-related DNA adducts were detected in in vitro and in vivo DNA samples.
• The method and database will help investigate the role of diet-related DNA adducts in diet-related chronic diseases.

Exposure of DNA to endo- and exogenous DNA binding chemicals can result in the formation of DNA adducts and is believed to be the first step in chemically induced carcinogenesis. DNA adductomics is a relatively new field of research which studies the formation of known and unknown DNA adducts in DNA due to exposure to genotoxic chemicals. In this study, a new UHPLC-HRMS(/MS)-based DNA adduct detection method was developed and validated. Four targeted DNA adducts, which all have been linked to dietary genotoxicity, were included in the described method; O6-methylguanine (O6-MeG), O6-carboxymethylguanine (O6-CMG), pyrimidopurinone (M1G) and methylhydroxypropanoguanine (CroG). As a supplementary tool for DNA adductomics, a DNA adduct database, which currently contains 123 different diet-related DNA adducts, was constructed. By means of the newly developed method and database, all 4 targeted DNA adducts and 32 untargeted DNA adducts could be detected in different DNA samples. The obtained results clearly demonstrate the merit of the described method for both targeted and untargeted DNA adduct detection in vitro and in vivo, whilst the diet-related DNA adduct database can distinctly facilitate data interpretation.

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