Molecular Structure of Chromium-DNA Adducts

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Chromium(VI) complexes are potent mutagens and carcinogens when inhaled, while the potential of these complexes to generate similar effects when taken orally is an area of active debate. The exact mechanism(s) of action of this activity is unknown, but potential mechanisms can be grouped into two categories. The first is mechanisms associated with the redox chemistry during the reduction of Cr(VI) ultimately to Cr(III). In the 20 years, significant progress has been made in characterizing alterations to DNA results from these redox processes. The second mechanism is based on the generated Cr(III) binding to DNA to form binary and ternary complexes, which ultimately give may arise to the mutagenic and carcinogenic effects. Unfortunately, while these Cr‐DNA complexes have been studied intensely the last circa 15 years, virtually no data on the molecular level structure of these Cr(III)‐DNA complexes exists. Such knowledge is essential to understanding and determining the potential of these complexes to lead to deleterious effects. Because of the unique magnetic and chemical properties of Cr(III) complexes, characterization of Cr(III)‐biomolecules is not trivial, requiring special expertise. Additionally, previous studies have used plasmid DNA, DNA polymers, calf thymus DNA, or DNA isolated from cultured cells, which because of their size and complexity present numerous potential Cr‐binding sites with a wide range of binding constants. What is required to determine the preferential sites for Cr‐binding and to characterize the structure of these sites is the use of DNA oligomers significantly smaller in size whose base sequences can be carefully designed and which can readily be synthesized in appreciable quantities and whose Cr(III) complexes are readily amendable to characterization by spectroscopic and magnetic techniques. Our long term goal is to characterize the binding of chromium(III) to DNA at a molecular level and relate the structures to the genotoxicity and carcinogenicity of Cr(VI).