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Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay
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Published on: November 10, 2013

Chromium(VI) but not chromium(III) species decrease mitoxantrone affinity to DNA.

Anna M Nowicka1, Zbigniew Stojek, Maria Hepel

  • 1Department of Chemistry, State University of New York at Potsdam, Potsdam, New York 13676, USA.

The Journal of Physical Chemistry. B
|January 9, 2013
PubMed
Summary

Chromium(VI) ions reduce the binding affinity of mitoxantrone (MXT) to DNA by oxidizing guanine, altering MXT-DNA interactions. Chromium(III) showed no effect on this drug-DNA binding process.

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Area of Science:

  • Biochemistry
  • Toxicology
  • Materials Science

Background:

  • Drug-DNA interactions are crucial for chemotherapy.
  • Chromium compounds are environmental pollutants with varying toxicities.
  • Understanding how metal ions affect drug-DNA binding is essential for predicting drug efficacy and toxicity.

Purpose of the Study:

  • To investigate the impact of Chromium(III) and Chromium(VI) on the binding of mitoxantrone (MXT) to double-stranded DNA.
  • To elucidate the mechanism by which chromium species influence MXT-DNA interactions.
  • To quantify changes in MXT-DNA binding affinity and site size in the presence of chromium.

Main Methods:

  • Spectroscopic techniques
  • Voltammetric analysis
  • Nanothermogravimetric measurements

Main Results:

  • Chromium(III) did not alter MXT-DNA binding affinity.
  • Chromium(VI) significantly decreased MXT-DNA binding affinity, from 1.96 × 10^5 M⁻¹ to 0.77 × 10^5 M⁻¹ at 30 μM Cr(VI).
  • Cr(VI) increased the MXT binding site size on DNA from 2 bp to 4-6 bp, suggesting guanine oxidation and disrupted intercalation.

Conclusions:

  • Chromium(VI) interferes with MXT-DNA intercalation, likely through guanine oxidation.
  • The study provides insights into the mechanism of chromium toxicity and its influence on drug-DNA interactions.
  • Multitechnique approach offers a comprehensive understanding of MXT-DNA-Cr interactions.