A COMPARISON OF HEPATIC-P450 INDUCTION IN RAT AND TROUT (ONCORHYNCHUS-MYKISS) - DELINEATION OF THE SITE OF RESISTANCE OF FISH TO PHENOBARBITAL-TYPE INDUCERS

1. A comprehensive approach was taken to delineate the site of refractivity of trout to phenobarbital-type (PB-type) hepatic monoxygenase (MO) inducers. 2. Model inducers β-naphthoflavone (BNF; 3-MC-type), and PB as well as the polychlorinated biphenyl isomers, 3,4,5,3',4',5'-hexachlorobiphenyl (3,4,5-HCB; 3-MC-type) and 2,4,5,2',4',5'-hexachlorobiphenyl (2,4,5-HCB; PB-type) were used to assess MO activities, total cytochromes P450, and [35S]-methionine incorporation into de novo synthesized microsomal protein in both trout and rats. 3. In rainbow trout immunodetection of P450§ § Throughout this paper, the suggested nomenclature for the P450 gene superfamily (Nebert et al., 1987, 1989) has been used except when reference is made to an earlier study where the original nomenclature is used. P450 inducers: β-naphthoflavone(BNF); 3,4,5, 3',4',5' hexachlorobiphenyl(PCB); 2,4,5,2',4',5' Hexachlorobiphenyl(PCB); phenobarbital(PB). isozymes and nucleic acid hybridization of rainbow trout P1450 mRNA using pfP1450-3' (trout 3-MC-inducible, P450IA1 gene) and genomic DNA using pfP1450-3' or pSP450-oligo (rat PB-inducible, P450IIB1 gene) cDNAs were carried out. 4. In rainbow trout, PB and 2,4,5-HCB do not increase hepatic MO activities, total cytochromes P450, de novo synthesis of microsomal protein, levels of P450 isozymes, or levels of P1450 mRNA. 5. Rainbow trout have, within their genome, DNA with sequence(s) similar to rat P450IIB1, but inducibility of this P450 in trout by PB-type inducers is lacking. © 1990.