Thiabendazole is an inducer of cytochrome P4501A1 in cultured rabbit hepatocytes.
The effect of TBZ (30-100 microM) was investigated on cytochromes P450 of cultured rabbit hepatocytes considered 72 h after plating. At the highest concentrations and without apparent cellular toxicity, the drug provokes a dose-dependent increase in total microsomal cytochrome P450 and a rise in EROD activity which was correlated to a specific increase in P4501A1 level. Northern blot analysis of RNA reveals an increased level of mRNA specific to P4501A1. The transcriptional activation of this isoenzyme is proposed because of the significant inhibition of the above-mentioned increases when actinomycin was added to the culture medium. Data obtained from competition experiments demonstrate that TBZ is not a ligand of Ah receptor. A down-regulation process could explain the slight decrease in both ANOH and P4502E1 level observed in hepatocytes treated with the highest dose of TBZ.
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Laboratoire de Pharmacologie-Toxicologie, INRA, Toulouse, France.
Rey-Grobellet
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Larrieu
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Lesca
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Galtier
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D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013827:Thiabendazole / Q000378:metabolism / Q000494:pharmacology*
D007527:Isoenzymes; D012333:RNA, Messenger; D003609:Dactinomycin; D003577:Cytochrome P-450 Enzyme System; D013827:Thiabendazole