title: Use of the rainbow trout cell lines, RTgill-W1 and RTL-W1 to evaluate the toxic potential of benzotriazoles.
abstract: Epithelial cell lines, RTgill-W1 and RTL-W1 from respectively gill and liver of rainbow trout, Onchorhynchus mykiss (Walbaum), were used to evaluate the toxic potential of six benzotriazoles (BTRs) and tolytriazole (TT), which is a commercial mixture of 4-methyl-1H-benzotriazole (4MBTR) and 5-methyl-1H-benzotriazole (5MBTR). The other BTRs were 1H-benzotriazole (1H-BTR), 5-chlorobenzotriazole (5CBTR), 1-hydroxybenzotriazole (1OHBTR) and 5,6-dimethyl-1H-benzotriazole monohydrate (DM). Except for DM, all BTRs were cytotoxic at concentrations above 15mg/L and transitorily elevated reactive oxygen species (ROS) levels. Neither N-acetyl cysteine (NAC) nor IM-54 inhibited cytotoxicity, suggesting that ROS were not the major cause of the cell death. Cell death was not blocked by Necrostatin nor accompanied by DNA laddering, suggesting that the cell death mechanism was neither necroptosis nor apoptosis. As judged by the comet assay, DNA strand breaks were detected with three BTRs: 4MBTR, 5MBTR and 5CBTR. In RTL-W1, the BTRs weakly induced cytochrome P4501A, suggesting that they have the potential to alter xenobiotic metabolism and activate the aryl hydrocarbon receptor. In summary, the toxic potential of BTRs appears to be limited to only high concentrations, which are higher than have been measured in the environment to date.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Fanxing
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Aquatic Contaminants Research Division, Environment Canada, Burlington, Ontario, Canada L7R 4A6.
authors.forename: James P
authors.initials: JP
authors.lastname: Sherry
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1. Electronic address: ncbols@uwaterloo.ca.
authors.forename: Niels C
authors.initials: NC
authors.lastname: Bols
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D020552:Comet Assay; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D005880:Gills / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods*; D014230:Triazoles / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D014230:Triazoles; C012771:benzotriazole; D003577:Cytochrome P-450 Enzyme System; C011852:1-hydroxybenzotriazole; C000594832:5-tolyltriazole
keywords: Benzotriazoles; Cytochrome P4501A; Cytotoxicity; Genotoxicity; Rainbow trout cells