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Constitutive and inducible expression of drug metabolizing enzymes in cultured human keratinocytes
Author(s) -
VECCHINI F.,
MACE K.,
MAGDALOU J.,
MAHE Y.,
BERNARD B.A.,
SHROOT B.
Publication year - 1995
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.1995.tb08618.x
Subject(s) - enzyme inducer , phenobarbital , enzyme , clofibrate , carcinogen , chemistry , cytochrome p450 , drug metabolism , reductase , methylcholanthrene , biochemistry , inducer , microbiology and biotechnology , biology , pharmacology , gene
Summary Drug metabolizing enzymes, particularly those involved in the metabolism of carcinogenic chemicals, were characterized in cultured human keratinocytes. Using immunoblotting experiments, we analysed the expression of phase I enzymes, cytochrome P4501A1 (CYP1A1) and NADPH reductase, and phase II enzymes, phenol UDP‐glucuronosyltransferase (UGT) and glutathione S‐transferase (GST) isoform pi, in the presence of either classical inducers (i.e. 3‐methyicholanthrene, dimethylbenz[a]anthracene, phenobarbital. and clofibrate) or all‐ trans retinoic acid (RA). This study has shown that the expression of CYP1A1 and UGT is concomitantly induced by 3‐methyIcholanthrene, 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 inducers. 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 CYP1A1 mRNA level. Our results indicate that, with the exception of clolibrate, xenobiotics and RA differentially modulate the expression of drug metabolizing enzymes.