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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
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DNA adductomics
Silvia Balbo1, Robert J Turesky, Peter W Villalta
1Department of Medicinal Chemistry and ‡The Masonic Cancer Center, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Chemical Research in Toxicology
|January 21, 2014
Summary
Systems toxicology integrates exposome data to understand health impacts. Advanced techniques like DNA adductomics using mass spectrometry are crucial for assessing lifetime exposures and biological responses.
Area of Science:
- Toxicology
- Biochemistry
- Environmental Health
Background:
- Systems toxicology aims to comprehensively understand biological responses to total exposures (exposome).
- Current methods for measuring DNA damage from daily exposures are limited.
- High-throughput 'omics' technologies are advancing systems toxicology.
Purpose of the Study:
- To explore the role of DNA adductomics in systems toxicology.
- To highlight the need for robust methods to measure DNA damage.
- To discuss the potential of mass spectrometry in assessing global DNA damage.
Main Methods:
- Review of systems toxicology principles and 'omics' tools.
- Discussion of DNA adductomics and its current limitations.
- Exploration of mass spectrometry (LC-MS(n)) for DNA adduct identification and quantification.
Main Results:
- DNA adductomics is an emerging field within systems toxicology.
- Mass spectrometry, especially high-resolution LC-MS(n), shows promise for global DNA damage assessment.
- Existing methods like (32)P-postlabeling have limitations in specificity and quantification.
Conclusions:
- Advanced analytical methods, particularly mass spectrometry, are essential for maturing DNA adductomics.
- DNA adductomics, alongside other 'omics' approaches, will significantly contribute to systems toxicology.
- Comprehensive assessment of the exposome and its impact on health requires robust DNA damage measurement techniques.
