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 CrO42- (Cr (VI)) and DNA. The sulfhydryl containing reagents included cysteine, glutathione, apo-metallothionein (apoMT). Zinc finger 3 of transcription factor IIIA (Z n-F-3) of Xenopus laevis was investigated as a potential redox active site of reaction of Cr (VI) and thiol compounds. The DNA samples were calf thymu s DNA and two oligomers, one of them specific for binding Zn-F-3. Results s howed that in the presence of Cr (VI) apoMT readily participated in damagin g 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 t hey, like apoMT, were able to reduce Cr (VI) to Cr (III) under the conditio ns 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 indica te that apoMT can effectively collaborate with Cr (VI) in reactions that ar e deleterious to DNA.