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Updated: Aug 17, 2026

Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
DNA adducts: mass spectrometry methods and future prospects
P B Farmer1, K Brown, E Tompkins
1Cancer Biomarkers and Prevention Group, Biocentre, University of Leicester, Leicester, LE1 7RH, UK. pbf1@le.ac.uk
Abstract:
Detection of DNA adducts is widely used for the monitoring of exposure to genotoxic carcinogens. Knowledge of the nature and amounts of DNA adducts formed in vivo also gives valuable information regarding the mutational effects that may result from particular exposures. The power of mass spectrometry (MS) to achieve qualitative and quantitative analyses of human DNA adducts has increased greatly in recent years with the development of improved chromatographic interfaces and ionisation sources. Adducts have been detected on nucleic acid bases, 2'-deoxynucleosides or 2'-deoxynucleotides, with LC-MS/MS being the favoured technique for many of these analyses. Our current applications of this technique include the determination of N7-(2-carbamoyl-2-hydroxyethyl)-guanine, which was postulated to be found as a DNA repair product in urine following exposure to acrylamide, and of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'-deoxyadenosine, as markers of oxidative damage in human lymphocyte DNA. Higher sensitivity (with a detection limit of 1-10 adducts/10(12) nucleotides) may be achieved by the use of accelerator mass spectrometry (AMS), although this requires the presence of certain isotopes, such as [(14)C], in the material being analysed. In order to make this technique more amenable for studies of human exposure to environmental carcinogens, new postlabelling techniques, incorporating [(14)C] into specific DNA adducts after formation, are being developed. It is expected that combining the use of advanced MS techniques with existing (32)P-postlabelling and immunochemical methodologies will contribute greatly to the understanding of the burden of human exposure to environmental carcinogens.
Insights
Detecting DNA adducts monitors exposure to genotoxic carcinogens. Advanced mass spectrometry (MS) techniques offer sensitive analysis of these adducts, aiding in understanding human exposure to environmental carcinogens.
Area of Science:
- Environmental Health Sciences
- Analytical Chemistry
- Molecular Biology
Background:
- DNA adduct detection is crucial for monitoring exposure to genotoxic carcinogens and understanding their mutagenic effects.
- Mass spectrometry (MS) has advanced significantly for qualitative and quantitative analysis of human DNA adducts.
- LC-MS/MS is a favored technique for adduct detection on nucleic acid bases, deoxynucleosides, or deoxynucleotides.
Purpose of the Study:
- To highlight the advancements in mass spectrometry (MS) for detecting and quantifying DNA adducts.
- To showcase applications of MS in identifying specific DNA adducts related to environmental exposures and oxidative damage.
- To discuss the development of new techniques for enhanced sensitivity in DNA adduct analysis.
Main Methods:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for analyzing DNA adducts.
- Accelerator mass spectrometry (AMS) for higher sensitivity detection (1-10 adducts/10^12 nucleotides) using isotopes like carbon-14.
- Development of new postlabelling techniques incorporating carbon-14 for broader applicability.
Main Results:
- Successful determination of N7-(2-carbamoyl-2-hydroxyethyl)-guanine as a urinary DNA repair product after acrylamide exposure.
- Identification of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydro-2'-deoxyadenosine as markers of oxidative damage in human lymphocyte DNA.
- Demonstration of enhanced sensitivity with AMS and ongoing development of new labelling techniques.
Conclusions:
- Advanced MS techniques, including LC-MS/MS and AMS, are powerful tools for analyzing DNA adducts.
- These methods provide critical insights into human exposure to environmental carcinogens and oxidative stress.
- Combining advanced MS with existing techniques like 32P-postlabelling and immunochemistry will significantly advance the understanding of human exposure burdens.
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