Carbaryl induces CYP1A1 gene expression in HepG2 and HaCaT cells but is not a ligand of the human hepatic Ah receptor
| Autor: | Pierre Lesca, G. de Sousa, C. Delescluse, Marcel Amichot, Madeleine Pralavorio, Roger Rahmani, Jean-Baptiste Bergé, N. Ledirac |
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| Přispěvatelé: | Laboratoire de biologie des invertébrés, Institut National de la Recherche Agronomique (INRA), Unité de recherche Pharmacologie-Toxicologie (UPT), ProdInra, Migration |
| Rok vydání: | 1997 |
| Předmět: |
Chloramphenicol O-Acetyltransferase
Insecticides [SDV]Life Sciences [q-bio] Pharmacology Toxicology Carbaryl Ligands Gene Expression Regulation Enzymologic Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P-450 CYP1A1 Humans RNA Messenger Enzyme inducer Receptor ComputingMilieux_MISCELLANEOUS 030304 developmental biology Regulation of gene expression Benzoflavones 0303 health sciences Reporter gene biology INDUCTION Cytochrome P450 respiratory system [SDV] Life Sciences [q-bio] HaCaT chemistry Biochemistry Receptors Aryl Hydrocarbon 030220 oncology & carcinogenesis biology.protein Methoxsalen Xenobiotic |
| Zdroj: | Toxicology and Applied Pharmacology Toxicology and Applied Pharmacology, Elsevier, 1997, 144 (1), pp.177-182 |
| ISSN: | 0041-008X 1096-0333 |
| Popis: | In spite of increasing numbers of insecticides used in agriculture, there are serious concerns regarding the potential risks of exposure to these agents. Carbaryl is one of the most important carbamate insecticides and has been used for about 30 years to control a wide range of pests. The study was designed to investigate if, among various insecticides currently used in world agriculture, this compound could induce human CYP1A1, an enzyme known to play an important role in the chemical activation of xenobiotics to genotoxic derivatives. Studies on HepG2 and HaCaT cell lines showed that carbaryl is capable of increasing, in a dose-dependent manner, both the ethoxyresorufin rufin-O-dec, O-deethylase activity and the steady-state concentrations of CYP1A1 mRNA, suggesting a transcriptional activation of this gene. When alpha-naphthoflavone, a partial Ah receptor (AhR) antagonist, and 8-methoxypsoralen, which interferes with the binding of activated AhR to the xenobiotic responsive element (XRE), were added to the cultures, CYP1A1 induction was suppressed. However, competitive binding studies using the 9S enriched fraction of human cytosol indicated that carbaryl did not displace [3H]TCDD from AhR. These data, together with the activation of a XRE-directed CAT reporter gene by carbaryl, suggest that induction of CYP1A1 involves the participation of the AhR and the XRE, but is not mediated by a direct carbaryl-receptor interaction. An alternative ligand-independent mechanism should be considered. Therefore, although carbaryl concentration in food is very low, care should be taken because of its possible adverse effects in human health through liver and skin, given the well established toxicological importance of CYP1A1 induction. |
| Databáze: | OpenAIRE |
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