title: MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone], a drinking-water carcinogen, does not induce mutations in the liver of cII transgenic medaka (Oryzias latipes).
abstract: Mutagenicity assays with Salmonella have shown that 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), a drinking-water disinfection by-product, is a potent mutagen, accounting for about one-third of the mutagenic potency/potential of chlorinated drinking water. The ability of MX to induce mutations was investigated in the liver of medaka (Oryzias latipes), a small fish model, utilizing the cII transgenic medaka strain that allows detection of in vivo mutations. Methylazoxymethanol acetate (MAMAc), a carcinogen in medaka, served as a positive control. Fish were exposed to MX at 0, 1, 10, or 30 mg/L for 96 h, whereas the MAMAc exposures were for 2 h at 0, 0.1, 1, or 10 mg/L. Both exposures were conducted under static water conditions and with fasted medaka. Following exposure, fish were returned to regular culture conditions to allow mutation expression for 15 or 40 d for MX or for 15 or 32 d for MAMAc. Mutations were not induced in medaka exposed to MX for 96 h. However, a concentration- and time-dependent increase in mutations was observed from the livers of fish exposed to 1 and 10 mg/L MAMAc. In conclusion, mutation induction was not observed in the livers of cII medaka exposed to MX for 96 h; however, studies are planned to examine mutation induction in the gills and skin to explore the possibility that MX-induced DNA damage occurs primarily in the tissues of initial contact.
authors.affiliation: Department of Coastal Sciences, Gulf Coast Research Laboratory, The University of Southern Mississippi, Ocean Springs, Mississippi, USA. dgeter@nc.rr.com
authors.forename: David R
authors.initials: DR
authors.lastname: Geter
authors.forename: Richard N
authors.initials: RN
authors.lastname: Winn
authors.forename: John W
authors.initials: JW
authors.lastname: Fournie
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Norris
authors.forename: Anthony B
authors.initials: AB
authors.lastname: DeAngelo
authors.forename: William E
authors.initials: WE
authors.lastname: Hawkins
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002273:Carcinogens / Q000633:toxicity*; D005663:Furans / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008746:Methylazoxymethanol Acetate / Q000633:toxicity; D009152:Mutagenicity Tests; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity; D009990:Oryzias / Q000235:genetics*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D005663:Furans; D019384:Nucleic Acid Synthesis Inhibitors; D014874:Water Pollutants, Chemical; D008746:Methylazoxymethanol Acetate; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone