Mass Spectrometric Mapping of the DNA Adductome as a Means to Study Genotoxin Exposure, Metabolism, and Effect
Lieselot Y Hemeryck1, Sharon A Moore2, Lynn Vanhaecke1
1Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University , Salisburylaan 133, Merelbeke, B-9820, Belgium.
Abstract:
Covalent binding of endo- or exogenous chemicals to DNA results in the formation of DNA adducts which are reflective of exposure of the human body to DNA-damaging molecules and their metabolic pathways. The study of DNA adduct types and levels in human tissue therefore offers an interesting tool in several fields of research, including toxicology and cancer epidemiology. Over the years, a range of techniques and methods have been developed to study the formation of endo- and exogenous DNA adducts. However, for the simultaneous detection, identification and quantification of both known and unknown DNA adducts, mass spectrometry (MS) is deemed to be the most promising technique. In this perspective, we focus on the analysis of multiple DNA adducts within a sample with the emphasis on untargeted analysis. The advantageous use of MS methodologies for DNA adductome mapping is discussed comprehensively with relevant field examples. In addition, several aspects of study design, sample pretreatment, and analysis are addressed as these factors significantly affect the reliability of DNA adductomics studies.
Insights
DNA adducts indicate exposure to DNA-damaging chemicals. Mass spectrometry (MS) is a powerful tool for simultaneously detecting and quantifying multiple DNA adducts, aiding toxicological and cancer research.
Area of Science:
- Environmental Toxicology
- Molecular Epidemiology
- Biomarker Discovery
Background:
- DNA adducts form from covalent binding of chemicals to DNA, reflecting exposure to harmful molecules.
- Studying DNA adducts in human tissues is crucial for toxicology and cancer epidemiology.
- Existing methods for DNA adduct analysis are limited in simultaneously detecting diverse adducts.
Purpose of the Study:
- To highlight mass spectrometry (MS) as the leading technique for simultaneous detection, identification, and quantification of DNA adducts.
- To emphasize the application of MS in untargeted DNA adductome mapping.
- To discuss critical factors influencing the reliability of DNA adductomics studies.
Main Methods:
- Focus on mass spectrometry (MS) for comprehensive DNA adduct analysis.
- Exploration of untargeted analysis for identifying both known and unknown DNA adducts.
- Discussion of study design, sample pretreatment, and analytical considerations.
Main Results:
- Mass spectrometry (MS) offers unparalleled capabilities for multi-adduct analysis.
- Untargeted MS approaches enable broad DNA adductome mapping.
- Optimized study design and sample handling are essential for reliable adductomics data.
Conclusions:
- MS is the most promising technique for simultaneous, comprehensive DNA adduct analysis.
- DNA adductome mapping using MS provides valuable insights into chemical exposures.
- Careful consideration of methodological aspects ensures the accuracy of DNA adductomics research.
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