ToxSci Advance Access published online on November 7, 2007
Toxicological Sciences, 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. 1200 Matsumoto, Kasugai 487-8501 Japan
Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502 Japan
Graduate School of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto, Kasugai 487-8501 Japan
Department of Environmental Bioresource, Ishikawa Prefectural University, 308-1 Suematsu, Nonoichi, Ishikawa 921-8836 Japan
¶ Corresponding author. Tel.& Fax: +81-568-51-6218. E-mail: miwa{at}isc.chubu.ac.jp
Received September 6, 2007; revision received November 2, 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 the 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 two-fold upregulated and 111 genes were downregulated. Upregulated genes included many that encode detoxification enzymes such as glutathione S-transferases (GST), UDP-glucuronosyl/glucosyl transferases (UGT), and short-chain type dehydrogenases (SDR) but only one cytochrome P450 (CYP). 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 two-fold upregulated by acrylamide treatment, their expression patterns were varied, and their regulation involved the transcription factor SKN-1 (a C. elegans homologue of Nrf1/2). We then selected the gst4::gfp-transformed C. elegans to study the detoxification rate of acrylamide and its metabolite glycidimide in living animals. This animal detects acrylamide as a 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.