Carcinogenic chromium(VI) induces cross-linking of vitamin C to DNA in vitro and in human lung A549 cells.

摘要: Reductive activation of carcinogenic Cr(VI) is required for the induction DNA damage and mutations. Here, we examined formation Cr−DNA adducts in reactions with its dominant biological reducer, vitamin C (ascorbate). conversion to Cr(III) by ascorbate produced stable adducts, which approximately 25% constituted ascorbate−Cr(III)−DNA cross-links. No evidence was found involvement Cr(V) or Cr(IV) intermediates either binary ternary adducts. The cross-linking reaction consistent attack transient Cr(III)−ascorbate complexes. yield Cr(III)−DNA similar on dsDNA AGT, ACT, CT oligonucleotides strongly inhibited Mg2+, suggesting predominant coordination phosphate oxygens. We also detected Cr(VI)-exposed human lung A549 cells that were preincubated dehydroascorbic acid create normal levels intracellular a...