Determination of genotoxic potential by comparison of structurally related azo dyes using DNA repair-deficient DT40 mutant panels. (December 2016) - Ooka, Masato
Abstract: Azo dyes, including Sudan I, Orange II and Orange G, are industrial dyes that are assumed to have genotoxic potential. However, neither the type of DNA damage induced nor the structural features responsible for toxicity have been determined. We used a panel of DNA-repair-pathway-deficient mutants generated from chicken DT40 cells to evaluate the ability of these azo dyes to induce DNA damage and to identify the type of DNA damage induced. We compared the structurally related azo dyes Sudan I, Orange II and Orange G to identify the structural features responsible for genotoxicity. Compared with wild type cells, the double-strand break repair defective RAD54 −/− /KU70 −/− cells were significantly more sensitive to Sudan I, but not to Orange II or Orange G. The quantum-chemical calculations revealed that Sudan I, but not Orange II or Orange G, has a complete planar aromatic ring structure. These suggest that the planar feature of Sudan I is critical to the inducing of double-strand breaks. In summary, we used a DNA-repair mutant panel in combination with quantum-chemical calculations to provide a clue to the chemical structure responsible for genotoxicity. Graphical abstract: Highlights: Sudan I showed a significant decrease in cell viability in DT40 RAD54 −/− /KU70 −/− cells compared with wild type cells. Orange II and Orange G did not exhibit enhanced cytotoxicity in any of the DT40 mutant cell lines tested. Sudan I induced chromosome aberrations in DT40 RAD54 −/− /KU70 −/− cells. The planar aromatic ring structure in Sudan I is the critical feature responsible for inducing DNA damage.