INDUCTION OF CYTOCHROME-P450 3A BY RETINOIDS IN RAT HEPATOCYTE CULTURE

1 Rat hepatocytes cultured on a Matrigel matrix were exposed for 48 h to all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid or fenretinide, 2 Cytochrome P450 3A (CYP3A) RNA levels were increased by approximately eightfold in hepatocytes treated with the retinoids compared to control cultures. 3 CYP1A1 and CYP1A2 RNA levels were only slightly affected or unaffected by the retinoids. 4 The induction of CYP3A by these therapeutically-useful retinoids suggests that they may share a common mechanism for accelerated drug catabolism and acquired clinical resistance.