3,3'-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices.
1. The effect of 3,3'-diindolylmethane (DIM), an indole derivative derived from cruciferous vegetables, on cytochrome P450 (CYP) isoforms in the CYP1A and CYP3A subfamilies has been studied in 72-h cultured human liver slices. 2. In cultured human liver slices 50 microM DIM induced 7-ethoxyresorufin O-deethylase and to a lesser extent 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 liver slice microsomes (dimethyl sulphoxide-only treated), DIM induced levels of CYP1A2 but had little effect on levels of CYP3A4. The treatment of human liver slices with 2 microg/ml of the polycholorinated biphenyl mixture Aroclor 1254 also resulted in an induction of levels of CYP1A2, but had no effect on CYP3A4. 4. These results demonstrate that DIM induces CYP1A isoforms in cultured human liver slices. Some variability in the magnitude of induction of enzyme activities by DIM was observed in four human liver samples examined. For 7-ethoxyresorufin O-deethylase, the magnitude of induction by 50 microM DIM ranged from 2.3- to 19.3-fold. 5. These results demonstrate that cultured human liver slices can be used to evaluate the effect of chemicals derived from cruciferous and other vegetables on CYP isoforms.
Lake
B G
BG
BIBRA International, Carshalton, UK.
Tredger
J M
JM
Renwick
A B
AB
Barton
P T
PT
Price
R J
RJ
D000293:Adolescent; D000328:Adult; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000187:drug effects; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000187:drug effects; D009924:Organ Culture Techniques
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007211:Indoles; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C016392:3,3'-diindolylmethane