Expression profile of human cells in culture exposed to glycidamide, a reactive metabolite of the heat-induced food carcinogen acrylamide
| Autor: | Flurina C. Clement, Ramiro Dip, Hanspeter Naegeli |
|---|---|
| Přispěvatelé: | University of Zurich, Naegeli, H |
| Rok vydání: | 2007 |
| Předmět: |
Hot Temperature
Metabolite Population Gene Expression Food Contamination Biology Toxicology medicine.disease_cause Transcriptome chemistry.chemical_compound Genes Reporter Cell Line Tumor medicine Humans education Carcinogen Oligonucleotide Array Sequence Analysis Acrylamide education.field_of_study Gene Expression Profiling NF-kappa B 3005 Toxicology 10079 Institute of Veterinary Pharmacology and Toxicology Glutathione Carcinogens Environmental chemistry Biochemistry Tumor progression Cancer research 570 Life sciences biology Epoxy Compounds Toxicogenomics Genotoxicity |
| Zdroj: | Toxicology. 240:111-124 |
| ISSN: | 0300-483X |
| Popis: | Recent findings of acrylamide in many common foods have sparked renewed interest in assessing human health hazards and the long-term risk associated with exposure to vinyl compounds. Acrylamide is tumorigenic at high doses in rodents and has been classified as a probable human carcinogen. However, cancer risk projections in the population remain problematic because the molecular pathogenesis of acrylamide at the low level of dietary uptake is not understood. In particular, the question of whether specific transcriptional responses may amplify or mitigate the known genotoxicity of acrylamide has never been examined. Here, we used high-density DNA microarrays and PCR validations to assess genome-wide messenger profiles induced by glycidamide, the more reactive metabolite of acrylamide. The expression changes resulting from glycidamide treatment of human epithelial cells are characterized by the induction of detoxification enzymes, several members of the glutathione system and antioxidant factors. Low-dose experiments indicate that the up-regulation of epoxide hydrolase 1 represents the most sensitive transcriptional biomarker of glycidamide exposure. At higher concentrations, glycidamide induces typical markers of tumor progression such as steroid hormone activators, positive regulators of nuclear factor-kappaB, growth stimulators and apoptosis inhibitors. Concomitantly, growth suppressors and cell adhesion molecules are down-regulated. The main implication of these findings for risk assessment is that low concentrations of glycidamide elicit cytoprotective reactions whereas transcriptional signatures associated with tumor progression may be expected only at doses that exceed the range of ordinary dietary exposures. |
| Databáze: | OpenAIRE |
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