Induction of CYP3A isoforms in cultured precision-cut human liver slices.
1. The effect of rifampicin on cytochrome P450 isoforms in the CYP1A and CYP3A subfamilies has been studied in 72-h cultured precision-cut human liver slices. 2. In cultured human liver slices 50 microM rifampicin induced testosterone 6 beta-hydroxylase activity, but had no effect on 7-ethoxyresorufin O-deethylase and 7-methoxyresorufin O-demethylase activities. 3. Western immunoblotting of liver slice microsomes was performed with antibodies to rat CYP1A2 and human CYP3A4. Compared with control (dimethyl sulphoxide only treated) liver slice microsomes, rifampicin increased levels of CYP3A4 but had no effect on CYP1A2. 4. These results demonstrate that rifampicin induces CYP3A isoforms, but not CYP1A2, in cultured human liver slices. Some variability in the magnitude of induction by rifampicin was observed in the six human liver samples examined. 5. These results demonstrate that cultured human liver slices may be used to evaluate the effects of xenobiotics on CYP3A isoforms.
Lake
B G
BG
BIBRA International, Carshalton, UK.
Ball
S E
SE
Renwick
A B
AB
Tredger
J M
JM
Kao
J
J
Beamand
J A
JA
Price
R J
RJ
D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D015153:Blotting, Western; D002648:Child; D046508:Culture Techniques; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis*; D012293:Rifampin / Q000494:pharmacology
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010089:Oxidoreductases, N-Demethylating; D012293:Rifampin