Model reactions of Cr (VI) with DNA mediated by thiol species.

Model reactions were devised to investigate the capacity of physiologically interesting thiol compounds to mediate reactions between CrO4(2-) (Cr (VI)) and DNA. The sulfhydryl containing reagents included cysteine, glutathione, apo-metallothionein (apoMT). Zinc finger 3 of transcription factor IIIA (Zn-F3) of Xenopus laevis was investigated as a potential redox active site of reaction of Cr (VI) and thiol compounds. The DNA samples were calf thymus DNA and two oligomers, one of them specific for binding Zn-F3. Results showed that in the presence of Cr (VI) apoMT readily participated in damaging DNA in a reaction that appeared to be hydroxyl radical dependent. It also became cross-linked to oligomer and native DNA samples. In comparison, the other two thiol donors were largely inactive in these assays even though they, like apoMT, were able to reduce Cr (VI) to Cr (III) under the conditions of the experiments. Direct attempts to cross link thiols with DNA in the presence of Cr3+ were unsuccessful at pH 7.4. Together, the results indicate that apoMT can effectively collaborate with Cr (VI) in reactions that are deleterious to DNA.