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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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A Comprehensive Database for DNA Adductomics.

Giorgia La Barbera1, Katrine Dalmo Nommesen1, Catalina Cuparencu1

  • 1Department of Nutrition Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark.

Frontiers in Chemistry
|June 13, 2022
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Summary

This study introduces a comprehensive DNA adducts database to improve the identification of DNA modifications. The database aids researchers in understanding carcinogenesis by providing a faster, more efficient tool for analyzing DNA adducts.

Keywords:
DNA adductcarcinogenesisdatabaseidentificationmass spectrometrytoxicology

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Area of Science:

  • Environmental Chemistry
  • Toxicology
  • Bioinformatics

Background:

  • Genotoxic compounds can cause DNA adducts, potentially leading to cancer.
  • DNA adductomics, using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), is emerging for adduct screening.
  • Current limitations in databases and bioinformatics tools hinder DNA adductomics applicability.

Purpose of the Study:

  • To develop and curate a comprehensive database for annotating DNA adducts in biological samples.
  • To enhance the efficiency and accuracy of DNA adduct identification in LC-HRMS analyses.
  • To provide insights into DNA modifications resulting from various genotoxicants.

Main Methods:

  • A four-step approach was used: literature review, structural harmonization, database expansion with new adducts, and spectral library construction.
  • Included literature-curated adducts identified by reference standards, NMR, or HRMS/MS.
  • Generated in silico MS/MS fragments and acquired experimental spectra for 15 reference standards.

Main Results:

  • A systematic database of 279 DNA adducts was compiled, harmonizing structures, formulas, and names.
  • The database was expanded to 582 entries, including 303 potential adducts with detailed chemical and structural information.
  • A preliminary spectral library with experimental and predicted MS/MS data was created.

Conclusions:

  • The publicly available DNA adducts database (https://gitlab.com/nexs-metabolomics/projects/dna_adductomics_database) is a valuable tool for (HR)MS data annotation.
  • Inclusion of metadata enhances prioritization and confidence in DNA adduct identification.
  • Future integration with authentic MS/MS spectra and user-friendly bioinformatics tools will further improve adduct identification.