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

Binding of mitoxantrone (MXT) to double-stranded DNA has been investigated as a model drug-DNA binding system to evaluate the effects of various forms of chromium on the binding properties. We have found that Cr(III), which binds strongly to DNA, does not affect the MXT affinity to DNA. In contrast, Cr(VI), in the form of chromate ions CrO(4)(2-), decreases the MXT affinity to DNA despite electrostatic repulsions with phosphate-deoxyribose chains of DNA. The MXT-DNA binding constant was found to decrease from (1.96 ± 0.005) × 10(5) to (0.77 ± 0.018) × 10(5) M(-1) for Cr(VI) concentration changing from 0 to 30 μM. The influence of Cr(VI) on MXT-DNA binding has been attributed to the oxidation of guanine residue, thus interrupting the intercalation of MXT into the DNA double helix at the preferential CpG intercalation site. This supposition is corroborated by the observed increase in the MXT binding site size from 2 bp (base pairs) to 4-6 bp in the presence of Cr(VI). The measurements of the MXT-DNA binding constant and the MXT binding site size on a DNA molecule have been carried out using spectroscopic, voltammetric, and nanogravimetric techniques, providing useful information on the mechanism of the interactions.

Citation

Anna M Nowicka, Zbigniew Stojek, Maria Hepel. Chromium(VI) but not chromium(III) species decrease mitoxantrone affinity to DNA. The journal of physical chemistry. B. 2013 Jan 31;117(4):1021-30

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PMID: 23293930

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