CONSTITUTIVE AND INDUCIBLE EXPRESSION OF DRUG-METABOLIZING-ENZYMES INCULTURED HUMAN KERATINOCYTES

Drug metabolizing enzymes, particularly those involved in the metaboli sm of carcinogenic chemicals, were characterized in cultured human ker atinocytes. Using immunoblotting experiments, we analysed the expressi on of phase I enzymes, cytochrome P4501A1 (CYP1A1) and NADPH reductase , and phase II enzymes, phenol UDP-glucuronosyltransferase (UGT) and g lutathione S-transferase (GST) isoform pi, in the presence of either c lassical inducers (i.e. 3-methylcholanthrene, dimethylbenz[a]anthracen e, phenobarbital, and clofibrate) or all-trans retinoic acid (RA). Thi s study has shown that the expression of CYP1A1 and UGT is concomitant ly induced by 3-methylcholanthrene, dimethylbenz[a]anthracene, and RA, and that of NADPH reductase is only enhanced by phenobarbital and RA. In contrast, the expression of GST pi was not affected by the inducer s. Using the reverse transcriptase-polymerase chain reaction, we have demonstrated that the effects of 3-methylcholanthrene, dimethylbenz[a] anthracene and RA on CYP1A1 expression correlate with an increase of C YP1A1 mRNA level. Our results indicate that, with the exception of clo fibrate, xenobiotics and RA differentially modulate the expression of drug metabolizing enzymes.