title: Evaluation of cII gene mutation in the brains of Big Blue mice exposed to acrylamide and glycidamide in drinking water.
abstract: Potential health risks for humans from dietary exposure to acrylamide (AA) and its reactive epoxide metabolite, glycidamide (GA), exist because substantial amounts of AA are found in a variety of fried and baked starchy foods. AA is tumorigenic in rodents, and a large number of studies indicate that AA is genotoxic in multiple organs of mice and rats. Although AA is neurotoxic, there are no reports on AA-induced gene mutations in the mouse brain. Therefore, to investigate if gene mutation can be induced by AA or its metabolite GA, we screened brains for cII mutant frequency (MF) and scored for mutation types in previously treated male and female Big Blue mice with 0, 1.4 mM, and 7.0 mM AA or GA in drinking water for up to 4 weeks. High doses of AA and GA induced similar cII MFs in males and females but only the induced cII MF in males was significantly higher than the corresponding male control MF (p < 0.05). Molecular analysis of the cII mutants from males showed that AA and GA each induced at least a 2.5-fold increase in the incidence of G:C → T:A, A:T → T:A, and A:T → C:G transversions compared to the vehicle controls, with similar mutational spectra observed when comparing AA with GA treatment. These results suggest that the MFs and types of mutations induced by AA and GA in the brain are consistent with AA exerting its genotoxicity via metabolism to GA.
authors.affiliation: Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, USA.
authors.forename: Hai-Fang
authors.initials: HF
authors.lastname: Li
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Shelton
authors.forename: Todd A
authors.initials: TA
authors.lastname: Townsend
authors.forename: Nan
authors.initials: N
authors.lastname: Mei
authors.forename: Mugimane G
authors.initials: MG
authors.lastname: Manjanatha
mesh_terms: D020106:Acrylamide / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008297:Male; D008822:Mice, Transgenic; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009154:Mutation; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D060766:Drinking Water; D004852:Epoxy Compounds; D014157:Transcription Factors; D014764:Viral Proteins; D014874:Water Pollutants, Chemical; C039000:cII protein, bacteriophage lambda; D020106:Acrylamide; C071834:glycidamide