title: Determination of genotoxic potential by comparison of structurally related azo dyes using DNA repair-deficient DT40 mutant panels.
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.
authors: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo, 192-0397, Japan.
authors: Masato
authors: M
authors: Ooka
authors: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo, 192-0397, Japan.
authors: Koji
authors: K
authors: Kobayashi
authors: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo, 192-0397, Japan.
authors: Takuya
authors: T
authors: Abe
authors: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo, 192-0397, Japan.
authors: Kazuhiko
authors: K
authors: Akiyama
authors: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo, 192-0397, Japan.
authors: Masahiko
authors: M
authors: Hada
authors: Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshidakonoe, Sakyo-ku, Kyoto, 606-8501, Japan.
authors: Shunichi
authors: S
authors: Takeda
authors: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo, 192-0397, Japan. Electronic address: khirota@tmu.ac.jp.
authors: Kouji
authors: K
authors: Hirota
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000737:chemistry / Q000633:toxicity*; D001557:Benzenesulfonates / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D002645:Chickens; D004396:Coloring Agents / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009284:Naphthols / Q000737:chemistry / Q000633:toxicity
chemical_list: D001391:Azo Compounds; D001557:Benzenesulfonates; D004396:Coloring Agents; D009153:Mutagens; D009284:Naphthols; C008710:Orange G; C024336:1-phenylazo-2-naphthol; C014722:2-naphthol orange
keywords: DNA damage; Genotoxicity; SAR; Structure-activity relationship; Sudan I