title: Sub-chronic exposure to 1,1-dichloropropene induces frameshift mutations in lambda transgenic medaka.
abstract: 1,1-Dichloropropene (1,1-DCP) is a contaminant present in both ground and surface waters used as sources for drinking water. Structural similarity to several compounds with known mutagenicity and carcinogenicity, and recent demonstration of mutagenicity in vitro, suggest this compound may be similarly mutagenic in vivo. A transgenic fish model, the lamda transgenic medaka, was used to evaluate the potential mutagenicity of this contaminant in vivo following sub-chronic exposure for 6 weeks. Mutant frequencies of the cII target gene (MF) increased six-fold in the livers of fish exposed to the lowest 1,1-DCP exposure concentration (0.44 mg/L, MF = 18.4 x 10(-5), and increased with each treatment, culminating in a 32-fold induction in fish from the highest 1,1-DCP treatment (16.60 mg/L, MF = 96.3 x 10(-5). Mutations recovered from treated fish showed a distinctive mutational spectrum comprised predominantly of +1 frameshift mutations, induced 166-fold above that of untreated animals. The majority of frameshifts were +1 insertions at thiamine and adenine. These results represent the first evidence of mutagenicity of 1,1-DCP in vivo, and of the highly characteristic spectrum of induced mutations dominated by +1 frameshift mutations. Based upon results from previous in vitro studies, the similar role of glutathione S-transferase (GSTT1-1) in the activation of 1,1-DCP to a mutagen in vivo is also suggested. This study further illustrates the utility of the lamda transgenic medaka as a model for identifying and characterizing potential genetic health risks associated with chemical exposures in the environment.
authors.affiliation: Aquatic Biotechnology and Environmental Laboratory, Warnell School of Forest Resources, University of Georgia, Athens, GA, USA. rwinn@uga.edu
authors.forename: Richard N
authors.initials: RN
authors.lastname: Winn
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Norris
authors.forename: Douglas
authors.initials: D
authors.lastname: Lothenbach
authors.forename: Kevin
authors.initials: K
authors.lastname: Flynn
authors.forename: Dean
authors.initials: D
authors.lastname: Hammermeister
authors.forename: Frank
authors.initials: F
authors.lastname: Whiteman
authors.forename: Barbara
authors.initials: B
authors.lastname: Sheedy
authors.forename: Rodney
authors.initials: R
authors.lastname: Johnson
mesh_terms: D000498:Allyl Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D010582:Bacteriophage lambda / Q000235:genetics*; D016368:Frameshift Mutation / Q000187:drug effects / Q000235:genetics*; D006843:Hydrocarbons, Chlorinated; D016296:Mutagenesis / Q000187:drug effects*; D009990:Oryzias / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; C500392:1,1-dichloropropene