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.
Jurima-Romet
M
M
Bureau of Drug Research, Drugs Directorate, Health Canada, Ottawa, Ontario, Canada.
Neigh
S
S
Casley
W L
WL
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects; D004790:Enzyme Induction; D007527:Isoenzymes / Q000096:biosynthesis* / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis* / Q000187:drug effects; D012313:RNA / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012176:Retinoids / Q000494:pharmacology*
D007527:Isoenzymes; D015345:Oligonucleotide Probes; D012176:Retinoids; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating