title: Acrylamide-responsive genes in the nematode Caenorhabditis elegans.
abstract: As acrylamide is a known neurotoxin for many animals and potential carcinogen for humans, it came as a surprise when the Swedish National Food Agency and Stockholm University reported in 2002 that it is formed during the frying or baking of foods. We report here genomic and proteomic analyses on genes and proteins of Caenorhabditis elegans exposed to 500 mg/l acrylamide. Of the 21,120 genes profiled, 409 genes were more than twofold upregulated and 111 genes were downregulated. Upregulated genes included many that encode detoxification enzymes such as glutathione S-transferases (GSTs), uridine diphosphate-glucuronosyl/glucosyl transferases, and short-chain type dehydrogenases but only one cytochrome P450. Subsequent proteomic analysis confirmed the heavy involvement of GSTs. Because of their high expression levels and central roles in acrylamide metabolism, we analyzed the in vivo expression patterns of eight gst genes. Although all encoded GST and were more than twofold upregulated by acrylamide treatment, their expression patterns were varied, and their regulation involved the transcription factor SKN-1 (a C. elegans homolog of Nuclear factor E2-related factors 1 and 2). We then selected the gst-4::gfp-transformed C. elegans to study the detoxification rate of acrylamide and its metabolite glycidimide in living animals. This animal detects acrylamide as a green fluorescence protein (GFP) expression signal in a dose- and time-dependent manner and may prove to be a useful tool not only for rapidly and inexpensively detecting acrylamide, a harmful substance in food, but also for analyzing mechanisms of GST induction by acrylamide and other inducers like oxidative stresses.
authors.affiliation: Institute for Biological Function, Chubu University, Kasugai 487-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Satsuki
authors.initials: S
authors.lastname: Miwa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Isomura
authors.forename: Kaname
authors.initials: K
authors.lastname: Tsutsumiuchi
authors.forename: Hajime
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Johji
authors.initials: J
authors.lastname: Miwa
mesh_terms: D020106:Acrylamide / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D004785:Environmental Pollutants; D049452:Green Fluorescent Proteins; D020106:Acrylamide; D005982:Glutathione Transferase