Regulation of hepatic cytochrome P4501A by indole-3-carbinol: transient induction with continuous feeding in rainbow trout.
This study investigated the kinetics of hepatic cytochrome P-4501A (CYP1A) induction in rainbow trout by indole-3-carbinol (I3C), a natural tumour modulator from cruciferous vegetables, and its low pH reaction products 3,3'-diindolylmethane (I33'), 5,6,11,12,17,18-hexahydrocyclononal[1,2-b:4,5-b':7,8-b"]triindo le cyclic trimer (CT), and the unresolved I3C acid reaction mixture (RXM). RXM, CT and I33' were potent inducers of total embryonic CYP1A following direct microinjection, and of fingerling hepatic CYP1A following ip exposure, whereas I3C itself produced only a transient and relatively weak induction. It is also reported for the first time that dietary I3C induced hepatic CYP1A and its associated ethoxyresorufin O-deethylase (EROD) activity in trout but, again, the induction was weak and transient even with continuous I3C feeding. Mechanism studies and mixed exposures with the Ah agonist beta-naphthoflavone indicated that transient induction by I3C was not due to diet ageing, but appears to involve inactivation of the Ah inductive pathway and irreversible inactivation of CYP1A-mediated EROD activity by I3C-derived metabolites. Thus, I3C derivatives exhibit dual capacities for CYP1A induction and inhibition in trout.
Takahashi
N
N
Department of Food Science and Technology, Oregon State University, Corvallis 97331.
Dashwood
R H
RH
Bjeldanes
L F
LF
Bailey
G S
GS
Williams
D E
DE
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D017686:Oncorhynchus mykiss; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D019324:beta-Naphthoflavone
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D001571:Benzoflavones; D007211:Indoles; D019324:beta-Naphthoflavone; C074140:5,6,11,12,17,18-hexahydrocyclononatriindole; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; C016392:3,3'-diindolylmethane