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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans
Byeong Hwa Yun1, Jingshu Guo1, Medjda Bellamri1
1Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN.
Abstract:
Hazardous chemicals in the environment and diet or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. In addition, reactive intermediates can be generated in the body through oxidative stress and damage the genome. The identification and measurement of DNA adducts are required for understanding exposure and the causal role of a genotoxic chemical in cancer risk. Over the past three decades, 32 P-postlabeling, immunoassays, gas chromatography/mass spectrometry, and liquid chromatography/mass spectrometry (LC/MS) methods have been established to assess exposures to chemicals through measurements of DNA adducts. It is now possible to measure some DNA adducts in human biopsy samples, by LC/MS, with as little as several milligrams of tissue. In this review article, we highlight the formation and biological effects of DNA adducts, and highlight our advances in human biomonitoring by mass spectrometric analysis of formalin-fixed paraffin-embedded tissues, untapped biospecimens for carcinogen DNA adduct biomarker research.
Insights
Detecting DNA adducts from environmental toxins is crucial for understanding cancer risk. Advanced mass spectrometry techniques now allow measurement in small human tissue samples, improving biomonitoring.
Area of Science:
- Environmental Health
- Molecular Biology
- Cancer Research
Background:
- Genomic DNA can form adducts with environmental hazardous chemicals or their metabolites.
- Oxidative stress can generate reactive intermediates, leading to genome damage.
- DNA adducts are key indicators of exposure and genotoxic chemical involvement in cancer initiation.
Purpose of the Study:
- To review the formation and biological effects of DNA adducts.
- To highlight advancements in human biomonitoring using mass spectrometry.
- To explore the potential of formalin-fixed paraffin-embedded tissues for biomarker research.
Main Methods:
- Established methods include 32P-postlabeling, immunoassays, GC/MS, and LC/MS.
- Liquid chromatography/mass spectrometry (LC/MS) enables adduct measurement in small human biopsy samples (milligrams).
- Mass spectrometric analysis of formalin-fixed paraffin-embedded tissues is a novel approach.
Main Results:
- Over three decades, various methods have been developed to assess chemical exposures via DNA adducts.
- LC/MS allows for sensitive detection of DNA adducts in limited human tissue.
- Formalin-fixed paraffin-embedded tissues represent an underutilized resource for carcinogen DNA adduct biomarker research.
Conclusions:
- Accurate measurement of DNA adducts is essential for assessing cancer risk from genotoxic exposures.
- Advances in mass spectrometry have significantly improved human biomonitoring capabilities.
- Formalin-fixed paraffin-embedded tissues offer a promising, untapped resource for future biomarker studies.
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