title: Human cell mutagenicity of chlorinated and unchlorinated water and the disinfection byproduct 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX).
abstract: Extracts of three water samples--humic acid-enriched water-both peatland water and drinking water, both with and without chlorination were tested for mutagenicity at the tk locus in MCL-5 cells, a line of human B-lymphoblastoid cells that express cytochrome P450 enzymes and microsomal epoxide hydrolase. Our results show that chlorination caused a 5.5-fold increase (P<0.0001) in the mutagenicity of the humic acid-enriched water. The unchlorinated peatland water was mutagenic at the two highest doses (240 and 480 microg equivalent total organic carbon (TOC)/ml), possibly due to polycyclic aromatic hydrocarbons (PAH) that were measured in the peat. In contrast, the chlorinated peatland water was non-mutagenic at low doses, while at the highest dose (240 microg equivalent TOC/ml) the sample was so toxic that an insufficient number of cells survived treatment to allow plating. The chlorinated and unchlorinated drinking water were both non-mutagenic. 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen and chlorine-disinfection byproduct, was also tested in MCL-5 cells as well as in two other human B-lymphoblastoid cell-lines, AHH-1 TK+/- and h1A1v2 cells, which differ from each other and from MCL-5 cells in the amounts of cytochrome P450 enzymes they can express. MX was mutagenic to all three cell-lines, but there was no apparent correlation between cytochrome P450 enzyme expression and the mutagenicity of MX. Overall, our results show that samples of chlorinated humic acid-enriched water and MX, a model chlorine-disinfection byproduct, are moderately mutagenic to human cells.
authors.affiliation: Department of Civil & Environmental Engineering, 018 Anderson Hall, Tufts University, Medford, MA 02155, USA.
authors.forename: N W
authors.initials: NW
authors.lastname: Woodruff
authors.forename: J L
authors.initials: JL
authors.lastname: Durant
authors.forename: L L
authors.initials: LL
authors.lastname: Donhoffner
authors.forename: B W
authors.initials: BW
authors.lastname: Penman
authors.forename: C L
authors.initials: CL
authors.lastname: Crespi
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D002460:Cell Line; D002713:Chlorine / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004202:Disinfectants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism; D005663:Furans / Q000633:toxicity*; D006801:Humans; D006812:Humic Substances / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D017354:Point Mutation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D018508:Water Purification; D014881:Water Supply / Q000032:analysis
chemical_list: D004202:Disinfectants; D005663:Furans; D006812:Humic Substances; D009153:Mutagens; D014874:Water Pollutants, Chemical; D002713:Chlorine; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D003577:Cytochrome P-450 Enzyme System; D013937:Thymidine Kinase; D004851:Epoxide Hydrolases