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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
Molecular Structure of Binary Chromium(III)-DNA Adducts
Silas Brown1, Molly M Lockart1, C Sumner Thomas1
1The University of Alabama, Department of Chemistry and Biochemistry, Box 870336, 250 Hackberry Lane, Tuscaloosa, AL, 43587-0336, USA.
Chromium(III) binds to DNA exclusively at guanine N7 positions. This study clarifies the molecular interactions of chromium(III) with DNA, crucial for understanding chromium carcinogenicity.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Biochemistry
Background:
- Chromium(VI) is a known carcinogen and mutagen.
- Its genotoxic effects are hypothesized to stem from its reduction product, chromium(III), binding to DNA.
- The precise molecular interactions of chromium(III) with DNA remain poorly understood.
Purpose of the Study:
- To elucidate the molecular-level binding site of chromium(III) on DNA.
- To investigate the interaction specificity of chromium(III) with DNA bases and backbone.
Main Methods:
- Analysis of oligonucleotide duplex DNA using Nuclear Magnetic Resonance (NMR) spectroscopy.
- Electron Paramagnetic Resonance (EPR) spectroscopy to study chromium interactions.
- Infrared (IR) spectroscopy to probe molecular binding.
Main Results:
- Chromium(III) metal centers exclusively interact with the N7 position of guanine residues.
- No evidence was found for chromium interactions with other DNA bases (adenine, cytosine, thymine).
- No interactions with the DNA backbone phosphates or formation of intra-strand crosslinks between guanine residues were observed.
Conclusions:
- The binding of chromium(III) to DNA is specific to the guanine N7 position.
- This finding provides a molecular basis for understanding the mechanisms of chromium-induced DNA damage and mutagenicity.
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