title: Identification of a new mutagenic polychlorinated biphenyl derivative in the Waka River, Wakayama, Japan, showing activation of an aryl hydrocarbon receptor-dependent transcription.
abstract: Water samples from the Waka River, which runs through an area housing many chemical industry facilities in Wakayama, Japan, have been found to show significant mutagenicity, especially without a mammalian metabolic activation system (S9 mix) in the Salmonella typhimurium YG1024 strain. Mutagens in the river water were adsorbed to 3 kg of blue cotton, extracted with methanol/ammonia, and separated by several low- and high-pressure liquid chromatography steps with reversed-phase columns. One mutagen (0.6 mg), accounting for 50% of the total mutagenicity of the adsorbed materials, was isolated. On the basis of the mass, high-resolution mass, (1)H NMR and (13)C NMR spectra, the chemical was determined to have a polychlorinated biphenyl skeleton with nitro and amino substitution groups. Well-designed chemical synthesis of the putative mutagen revealed it to be 4-amino-3,3'-dichloro-5,4'-dinitrobiphenyl. This novel compound exerted strong mutagenicity without the S9 mix, inducing 66,000 and 140,000 revertants/nmol in S. typhimurium TA98 and YG1024, respectively. Moreover, this polychlorinated biphenyl derivative was proven to activate the human aryl hydrocarbon receptor-mediated transcription in a lac Z reporter gene assay with an efficiency almost the same as that of beta-naphthoflavone, well-known to be a synthetic aryl hydrocarbon receptor agonist. It is possible that the mutagen is formed unintentionally via postemission modification of drainage water containing parent chemicals, such as 3,3'-dichlorobenzidine or 3,3'-dichloro-4,4'-dinitrobiphenyl, which are known to be raw materials in the manufacture of polymers and dye intermediates in chemical plants.
authors.affiliation: Cancer Prevention Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-Ku, Tokyo 104-0045, Japan. tenya@gan2.ncc.go.jp
authors.forename: Takeji
authors.initials: T
authors.lastname: Takamura-Enya
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tada
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Hirayama
authors.forename: Haruo
authors.initials: H
authors.lastname: Nukaya
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugimura
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D002617:Chemical Industry; D004136:Dinitrobenzenes / Q000032:analysis; D007564:Japan; D009682:Magnetic Resonance Spectroscopy; D009152:Mutagenicity Tests; D009153:Mutagens / Q000032:analysis* / Q000302:isolation & purification; D011078:Polychlorinated Biphenyls / Q000032:analysis* / Q000302:isolation & purification / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012486:Salmonella typhimurium; D014158:Transcription, Genetic; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000302:isolation & purification / Q000633:toxicity
chemical_list: D004136:Dinitrobenzenes; D009153:Mutagens; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls