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 (CY P1A) 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'), hexahydrocyclononal[1,2-b:4,5-b ':7,8-b'']triindole cyclic trimer (CT), and the unresolved I3C acid re action mixture (RXM). RXM, CT and I33' were potent inducers of total e mbryonic CYP1A following direct microinjection, and of fingerling hepa tic CYP1A following ip exposure, whereas I3C itself produced only a tr ansient and relatively weak induction. It is also reported for the fir st time that dietary I3C induced hepatic CYP1A and its associated etho xyresorufin O-deethylase (EROD) activity in trout but, again, the indu ction was weak and transient even with continuous I3C feeding. Mechani sm 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 i rreversible inactivation of CYP1A-mediated EROD activity by DC-derived metabolites. Thus, I3C derivatives exhibit dual capacities for CYP1A induction and inhibition in trout.