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 (CYPlA) 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″]triindole cyclic trimer (CT), and the unresolved I3C acid reaction mixture (RXM). RXM, CT and I33′ were potent inducers of total embryonic CYPlA following direct microinjection, and of fingerling hepatic CYPlA following ip exposure, whereas 13C itself produced only a transient and relatively weak induction. It is also reported for the first time that dietary 13C induced hepatic CYPlA 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 β-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 CYPlA-mediated EROD activity by I3C-derived metabolites. Thus, I3C derivatives exhibit dual capacities for CYPlA induction and inhibition in trout.