Human cell mutagenicity of chlorinated and unchlorinated water and the disinfection byproduct 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX)

Mutat Res. 2001 Aug 22;495(1-2):157-68. doi: 10.1016/s1383-5718(01)00243-1.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / enzymology
  • Cell Line
  • Chlorine / toxicity*
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Disinfectants / toxicity*
  • Dose-Response Relationship, Drug
  • Epoxide Hydrolases / genetics
  • Epoxide Hydrolases / metabolism
  • Furans / toxicity*
  • Humans
  • Humic Substances / toxicity
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Point Mutation
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Water Pollutants, Chemical / toxicity*
  • Water Purification
  • Water Supply / analysis

Substances

  • Disinfectants
  • Furans
  • Humic Substances
  • Mutagens
  • Water Pollutants, Chemical
  • Chlorine
  • 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone
  • Cytochrome P-450 Enzyme System
  • Thymidine Kinase
  • Epoxide Hydrolases