Synthesis and analysis of DNA chromium complexes

Studies have shown that the key step, in the carcinogenicity and toxicity of Cr(VI) compounds is its intracellular reduction to Cr(III). The Cr(III) so produced causes the formation of DNA-Cr-Protein (DCP) crosslinks, which have been implicated in the initiation of carcinogenesis due to their persistence. The purpose of this project was to develop methods for the synthesis of Cr(III)-DNA complexes and their analysis. The complexes that were prepared were, DNA-Cr(III) by the method of reduction, and DNA-Cr(III), DNA-Cr(III) bipyridyl, and DNA-Cr(III) o-phenanthroline, prepared by direct substitution. The effects of concentration, temperature, dropping rate of the reductant, time, and ionic strength on the reaction, were also studied. The DNA-Cr(III) complexes that were formed were oxidized and the metal concentration was determined using a spectrophotometric method. The reduction method gives a chromium to base ratio of 1.90 and the substitution method gives a ratio of 0.61. The complexes are digested enzymatically and separated using HPLC.