title: In vitro investigation of toxaphene genotoxicity in S. typhimurium and Chinese hamster V79 lung fibroblasts.
abstract: The polychlorinated pesticide toxaphene has been identified as a persistent environmental contaminant and is of particular concern in the Great Lakes and Arctic regions of Canada. Inconsistencies in published in vitro genotoxicology studies have hindered risk assessments of toxaphene exposure. When toxaphene mutagenicity was re-evaluated in the Ames Salmonella/microsome assay at 10-10,000 microg/plate, a dose-dependent increase in His revertants occurred in all five strains of S. typhimurium tested (TA97, TA98, TA100, TA102 and TA104) with higher mutation frequencies observed in the absence of S9 metabolic activation. However, the mutagenic potential of toxaphene was relatively low with concentrations greater than 500 microg/plate required to induce mutation. Toxaphene genotoxicity was also examined in a mammalian system using Chinese hamster V79 lung fibroblasts with metabolic activation provided by human HepG2 hepatoma cells. Genotoxicity of 1-10 microg/ml toxaphene was examined by measuring the frequency of sister chromatid exchange (SCE) and mutation induction at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) gene locus. Although small increases in SCE were observed at toxic concentrations of toxaphene approaching the LD50 (10 microg/ml), they were not found to be statistically significant relative to control. Toxaphene was also unable to induce HGPRT mutagenesis at the concentrations tested. These results show that while toxaphene is a weak, direct-acting mutagen in the Ames Salmonella Test, convincing evidence of dose-dependent SCE induction and mutagenicity at the HGPRT gene locus could not be demonstrated in V79 cells.
authors.affiliation: Toxicology Research Division, Food Directorate, Health Canada, Ottawa, Ontario, Canada. tim_schrader@hc-sc.gc.ca
authors.forename: T J
authors.initials: TJ
authors.lastname: Schrader
authors.forename: B G
authors.initials: BG
authors.lastname: Boyes
authors.forename: T I
authors.initials: TI
authors.lastname: Matula
authors.forename: C
authors.initials: C
authors.lastname: Héroux-Metcalf
authors.forename: I
authors.initials: I
authors.lastname: Langlois
authors.forename: R H
authors.initials: RH
authors.lastname: Downie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects*; D012854:Sister Chromatid Exchange / Q000187:drug effects; D014112:Toxaphene / Q000633:toxicity*
chemical_list: D009153:Mutagens; D014112:Toxaphene; D007041:Hypoxanthine Phosphoribosyltransferase