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 beta-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 isozymes and nucleic acid hybridization of rainbow trout P(1)450 mRNA using pfP(1)450-3' (trout 3-MC-inducible, P450IA1 gene) and genomic DNA using pfP(1)450-3' 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 P(1)450 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.
Kleinow
K M
KM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Haasch
M L
ML
Williams
D E
DE
Lech
J J
JJ
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004247:DNA / Q000302:isolation & purification; D004351:Drug Resistance / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism; D013045:Species Specificity; D014337:Trout / Q000378:metabolism*
D007527:Isoenzymes; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital