ToxSci Advance Access originally published online on November 7, 2007
Toxicological Sciences 2008 101(2):215-225; doi:10.1093/toxsci/kfm276
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Acrylamide-Responsive Genes in the Nematode Caenorhabditis elegans
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* Institute for Biological Function, Chubu University, Kasugai 487-8501, Japan
Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai 487-8501, Japan
Department of Environmental Bioresource, Ishikawa Prefectural University, Ishikawa 921-8836, Japan
1 To whom correspondence should be addressed. Johji Miwa, Graduate School of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto, Kasugai 487–8501, Japan. Fax: +81-568-51-6218. E-mail: miwa{at}isc.chubu.ac.jp.
Received September 6, 2007; accepted November 2, 2007
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Abstract |
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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.
Key Words: xenobiotics; Phase II enzymes; biomarkers; food safety; toxicogenomics; proteomics.