Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, 9820, Belgium.
Division of Digestive Oncology, Department of Gastroenterology, University Hospital Ghent, De Pintelaan 185, Ghent, 9000, Belgium.
Anal Chim Acta. 2015 Sep 10;892:123-31. doi: 10.1016/j.aca.2015.08.019. Epub 2015 Aug 22.
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.
DNA 暴露于内源性和外源性 DNA 结合化学物质会导致 DNA 加合物的形成，这被认为是化学诱导致癌作用的第一步。DNA 加合物组学是一个相对较新的研究领域，研究由于暴露于遗传毒性化学物质而在 DNA 中形成的已知和未知的 DNA 加合物。在这项研究中，开发并验证了一种新的基于 UHPLC-HRMS(/MS)的 DNA 加合物检测方法。该方法包括四种已被证明与饮食遗传毒性相关的靶向 DNA 加合物：O(6)-甲基鸟嘌呤（O(6)-MeG）、O(6)-羧甲基鸟嘌呤（O(6)-CMG）、嘧啶嘌呤酮（M1G）和甲基羟丙基鸟嘌呤（CroG）。作为 DNA 加合物组学的补充工具，构建了一个 DNA 加合物数据库，其中目前包含 123 种不同的与饮食相关的 DNA 加合物。通过新开发的方法和数据库，可以在不同的 DNA 样本中检测到所有 4 种靶向 DNA 加合物和 32 种非靶向 DNA 加合物。获得的结果清楚地证明了该方法在体外和体内用于靶向和非靶向 DNA 加合物检测的优势，而饮食相关的 DNA 加合物数据库可以明显促进数据解释。
