Induction of two immunochemically related rat liver cytochrome P-450 isozymes, cytochromes P-450c and P-450d, by structurally diverse xenobiotics.
We have previously shown that purified rat liver cytochromes P-450c and P-450d share some but not all immunochemical determinants (Reik, L. M., Levin, W., Ryan, D.E., and Thomas, P.E. (1982) J. Biol. Chem. 257, 3950-3957). Antibody to cytochrome P-450d cross-reacts with cytochrome P-450c to form an immunoprecipitin band in the Ouchterlony test, but no detectable immunoprecipitin ring is formed in a radial immunodiffusion assay. However, the addition of purified cytochrome P-450c to purified cytochrome P-450d in the radial immunodiffusion assay alters the cytochrome P-450d standard curve. Appropriate corrections have been made for the interference of cytochrome P-450c in the immunoquantitation of cytochrome P-450d. Twelve structurally diverse xenobiotics have been examined for their capacity to modulate the levels of cytochrome P-450d, as well as cytochromes P-450a, P-450b, and P-450c, in rat liver microsomes. Five compounds (isosafrole, 3-methylcholanthrene, beta-naphthoflavone, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and phenothiazine) and the polychlorinated biphenyl mixture Aroclor 1254 are potent in vivo inducers of cytochrome P-450d (0.44-0.89 nmol of cytochrome P-450d/mg of microsomal protein). Control rats have low levels of this microsomal hemoprotein (0.04-0.05 nmol of cytochrome P-450d/mg of microsomal protein). Isosafrole induces cytochrome P-450d to a greater extent than cytochrome P-450c, Aroclor 1254 induces both hemoproteins to similar extents, and the remaining four compounds preferentially induce cytochrome P-450c relative to cytochrome P-450d. All of these structurally diverse compounds induce cytochromes P-450d and P-450c, suggesting that the inducibility of these cytochrome P-450 isozymes, but not cytochromes P-450a and P-450b, is linked.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004790:Enzyme Induction; D007106:Immune Sera; D005779:Immunodiffusion; D007536:Isomerism; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D011863:Radioimmunoassay; D051381:Rats; D012451:Safrole / Q000494:pharmacology
D007106:Immune Sera; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D012451:Safrole; C015959:isosafrole