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Examining the Potential Formation of Ternary DNA Complexes with Chromium‑Cysteine, Chromium-Ascorbate, and Chromium-Glutathione and Implications for Their Carcinogenicity

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Abstract

The mutagenic and carcinogenic properties of chromium(VI) complexes have been ascribed to the formation of ternary Cr(III)-small molecule-DNA complexes. As part of these laboratories’ efforts to establish the structure and properties of discrete binary and ternary adducts of Cr(III) and DNA at a molecular level, the properties of Cr(III)-cysteine-DNA, Cr(III)-ascorbate-DNA, and Cr(III)-glutathione-DNA complexes formed from Cr(III) were examined. These studies determined the composition of previously described “pre-reacted” chromium cysteinate and chromium glutathione. Neither of these complexes nor “chromium ascorbate” form ternary complexes with DNA as previously proposed. In fact, these Cr(III) compounds do not measurably bind to DNA and cannot be responsible for the mutagenic and carcinogenic properties ascribed to ternary Cr(III)-cysteine-DNA and Cr(III)-ascorbate-DNA adducts. The results of biological studies where “ternary adducts” of Cr(III), cysteine, glutathione, or ascorbate and DNA were made from “pre-reacted” chromium cysteinate or chromium glutathione or from “chromium ascorbate” must, therefore, be interpreted with caution.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We also thank the NSF MRI program (CHE1919906) for the purchase of the 500 MHz NMR spectrometer.

Funding

This work was supported by the National Institutes of Health, R15ES033800 (to J.B.V and S.A.W) and the Bioinorganic Chemistry of Chromium Research Fund of The University of Alabama.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The University of Alabama, Tuscaloosa, AL, 35487-0336, USA

    Sydney Marchi, Emma Lankford, Bradley Dorin, Eilidh Drummond, Sumner C. Thomas, Stephen A. Woski & John B. Vincent

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  1. Sydney Marchi
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  2. Emma Lankford
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  3. Bradley Dorin
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  4. Eilidh Drummond
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  5. Sumner C. Thomas
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  6. Stephen A. Woski
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  7. John B. Vincent
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Contributions

John B. Vincent: Conceptualization, Writing- Original Manuscript, Reviewing and Editing. Sydney Marchi: Investigation. Bradley Dorin: Investigation. Eilidh Drummond: Investigation. C. Sumner Thomas: Investigation. Stephen A. Woski: Conceptualization, Formal analysis, Writing- Reviewing and Editing. All authors reviewed the manuscript.

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Correspondence to John B. Vincent.

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Marchi, S., Lankford, E., Dorin, B. et al. Examining the Potential Formation of Ternary DNA Complexes with Chromium‑Cysteine, Chromium-Ascorbate, and Chromium-Glutathione and Implications for Their Carcinogenicity. Biol Trace Elem Res 201, 5053–5066 (2023). https://doi.org/10.1007/s12011-023-03573-8

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