title: High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts.
abstract: 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; O(6)-methylguanine (O(6)-MeG), O(6)-carboxymethylguanine (O(6)-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.
authors.affiliation: Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, 9820, Belgium.
authors.forename: Lieselot Y
authors.initials: LY
authors.lastname: Hemeryck
authors.affiliation: Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, 9820, Belgium.
authors.forename: Anneleen I
authors.initials: AI
authors.lastname: Decloedt
authors.affiliation: Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, 9820, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Vanden Bussche
authors.affiliation: Division of Digestive Oncology, Department of Gastroenterology, University Hospital Ghent, De Pintelaan 185, Ghent, 9000, Belgium.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Geboes
authors.affiliation: Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, 9820, Belgium. Electronic address: Lynn.Vanhaecke@ugent.be.
authors.forename: Lynn
authors.initials: L
authors.lastname: Vanhaecke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000032:analysis*; D062126:Databases, Chemical; D004032:Diet; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry
chemical_list: D018736:DNA Adducts; D006147:Guanine; D004247:DNA; C427203:calf thymus DNA; C008449:O-(6)-methylguanine
keywords: Colorectal cancer; Deoxyribonucleic acid adduct database; Dietary chemicals; High resolution mass spectrometry; Quadrupole-Orbitrap