THIABENDAZOLE IS AN INDUCER OF CYTOCHROME P4501A1 IN CULTURED RABBIT HEPATOCYTES

The effect of TBZ (30-100 mu M) was investigated on cytochromes P450 o f cultured rabbit hepatocytes considered 72 h after plating. At the hi ghest 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 increa se in P4501A1 level. Northern blot analysis of RNA reveals an increase d level of mRNA specific to P4501A1. The transcriptional activation of this isoenzyme is proposed because of the significant inhibition of t he above-mentioned increases when actinomycin was added to the culture medium. Data obtained from competition experiments demonstrate that T BZ is not a ligand of Ah receptor. A down-regulation process could exp lain the slight decrease in both ANOH and P4502E1 level observed in he patocytes treated with the highest dose of TBZ. (C) 1994 Academic Pres s, Inc.