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High resolution mass spectrometry based profiling of diet-related deoxyribonucleic acid adducts
Lieselot Y Hemeryck1, Anneleen I Decloedt1, Julie Vanden Bussche1
1Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, 9820, Belgium.
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.
Insights
Researchers developed a new method to detect DNA adducts, which are linked to cancer. This technique, alongside a DNA adduct database, successfully identified known and unknown adducts in DNA samples, aiding carcinogenicity research.
Area of Science:
- Toxicology
- Molecular Biology
- Analytical Chemistry
Background:
- DNA adducts form from chemical exposure and are implicated in chemical carcinogenesis.
- DNA adductomics is an emerging field for identifying DNA adducts from genotoxic chemical exposure.
Purpose of the Study:
- To develop and validate a novel UHPLC-HRMS(/MS)-based method for DNA adduct detection.
- To construct a DNA adduct database to support DNA adductomics research.
- To detect targeted and untargeted DNA adducts in vitro and in vivo.
Main Methods:
- Development and validation of a UHPLC-HRMS(/MS) method.
- Inclusion of four targeted DNA adducts: O(6)-methylguanine (O(6)-MeG), O(6)-carboxymethylguanine (O(6)-CMG), pyrimidopurinone (M1G), and methylhydroxypropanoguanine (CroG).
- Construction of a DNA adduct database with 123 diet-related DNA adducts.
Main Results:
- The new method successfully detected all 4 targeted DNA adducts.
- 32 untargeted DNA adducts were also identified in DNA samples.
- The method demonstrated effectiveness for both targeted and untargeted DNA adduct detection.
Conclusions:
- The developed UHPLC-HRMS(/MS) method is highly effective for DNA adductomics.
- The DNA adduct database significantly aids in interpreting results from DNA adduct detection.
- This integrated approach advances the study of diet-related genotoxicity and carcinogenesis.
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