| Hexavalent chromium is a known carcinogen that is found in many different industrial processes, such as chromium refining, leather tanning, chromate pigment production, chrome plating, welding and the producing of tobacco products. Since chromium(VI) is widely used, people can be exposed to it for long periods of time. Organic carcinogens such as benzene, naphthalene, aromatic amines and BPA are also found in occupational processes; therefore, the occurrence of a co-exposure to more than one chemical at a time is potentially elevated. Chromate has historically been used as an oxidizing agent for organic compounds; therefore, we propose that it has the potential to activate organic carcinogens to DNA-reactive intermediates in the absence of metabolizing enzymes. We hypothesize that if there is a direct reaction between chromium(VI) and the organic molecule, then the dominant type of DNA damage observed would be adducts or strand breaks, and there would also be an increase in the amount of DNA damage formed relative to individual exposures. This hypothesis was tested by reacting chromium(VI) in the presence of plasmid DNA with various organic molecules in the absence of metabolizing enzymes. Reactions were analyzed by gel electrophoresis to detect single strand breaks and piperidine-sensitive covalent DNA adducts. The reaction of chromium(VI) with hydroquinone, a metabolite of benzene, was shown to have a significant increase in plasmid DNA damage relative to reactants alone. The interaction of hydroquinone and chromium was confirmed by UV-visible spectroscopy, and the purity of hydroquinone was verified using ¹H NMR spectroscopy. Three metabolites of naphthalene were tested, and both 1- and 2-naphthol did not cause DNA damage. The third metabolite, 1,4-naphthoquinone, produced low levels of DNA damage but showed no dose response to increasing concentrations of chromium(VI). It was determined from UV-visible spectroscopy that naphthoquinone was reduced by HEPES buffer, which allowed for the oxidation by chromium(VI) leading to DNA damage, which was further supported by ¹H NMR spectroscopy. Three aromatic amines were also tested: 1,2-naphthylamine, 4-aminobiphenyl, and benzidine. No reaction was observed with DNA when these amines were mixed with chromium(VI). The last compound tested, bisphenol A, showed no reaction in the DNA when combined with chromium(VI). |
