Cytochrome type inducers

These agents seem to induce hemoprotein(s) P-450 which possess properties in common with both the phenobarbital-and 3-methylcholanthrene- type inducers. Hence, it would appear that multiple forms of cytochrome P-450 and cytochrome P -4S0 exist. 

Studies utilizing barbituate-type inducing agents have generally indicated that fish may be refractive to cytochrome P-450 type of inducers (16,22,26). 

In summary, it would appear that rainbow trout are responsive to cytochrome P -450-type inducers (e.g. planar polychlorinated biphenyls and polycyclic aromatic hydrocarbons), but are not responsive to cytochrome P-450-type inducers (e.g. phenobar-bital and non-planar polychlorinated biphenyls). Although induced rainbow trout hemoprotein(s) P-450 show high activity with cytochrome P -450 substrates, the induced hemoprotein at 57,000 daltons appears, in electrophoretic and spectral properties, to differ from rodent cytochrome P -450. 

The ability of PBBs to induce hepatic Phase I xenobiotic metabolizing enzymes (cytochrome P-450-dependent monooxygenases) is well documented (Dannan et al. 1978b, 1982a, 1982b, 1983 Ecobichon et al. 1979 Moore et al. 1978, 1979 Parkinson et al. 1983 Robertson et al. 1982 Schramm et al. 1985). PBB mixtures were classified as "mixed-type" inducers of hepatic microsomal monooxygenases and... 

There are basically three types of cytochrome P450 inducers (1) phenobarbital-like (the major class) (2) methylcholanthrene-like (which actually increases a P448 isozyme) and (3) anabolic steroids. The former two have been the most frequently studied. Research over the past 40-50 years indicates that their mechanism of action involves genetic interaction, possibly via derepression of a repressor gene, and the subsequent synthesis of mRNA for the specific enzyme proteins. Examples of phenobarbital-like enzyme inducers, the most common, are shown in Table 3.6. 

TOEI type of enzyme induction (1) PB-type Phenobarbital inducer induction of cytochrome P450 lA (CYPIA). (2) MC-type 3-Methylcholanthrene type inducer induction of cytochrome P450 2B (CYP2B). (3) Mixed-type some of both PB- and MC-type inducers mixed CYP1A/CYP2B induction. 

Arylhydrocarbon Hydroxylase. Benzo(a)pyrene (BaP) is considered an ideal model compound for monitoring arylhydrocarbon hydroxylase (AAH) MFO levels in rats. Its metabolism has been widely investigated in both rat liver and extrahepatic tissues (40-41,61 -70). Arylhydrocarbon hydroxylase has been compared to biphenyl hydroxylase in the intestines of rats (25,28). Intestinal AAH has been shown to be induced up to 30-fold with cytochrome P-448-type inducers, while being insensitive to P-450-type induction. Therefore, we have used intestinal AAH in conjunction with biphenyl hydroxylation, to evaluate the effects of dietary fibers on intestinal metabolism. 

Epoxide Hydrolase. Epoxide hydrolase (EH) activity has been studied in numerous tissues with many different substrates (71-72). Hepatic microsomal EH has been shown to be induced by polycyclic aromatic hydrocarbons, but is insensitive to cytochrome P-450 type inducers (73). Epoxide hydrolase has been related to the activation of polycyclic aromatic hydrocarbons into reactive carcinogens (70). Epoxide hydrolase activity has been determined... 

Abbreviations NADPH-cytochrome c reductase activity (P-450R), radiometric BPH assay (BPH-R), fluorometric BPH assay (BPH-F), 3-methylcholanthrene (3MC), benzo[a]pyrene (BaP), phenobarbital (PB), 3,4,3 4 -tetrachlorobiphenyl (3MC-type inducer) (3,4,3 4 -TCBP), 2,4,5,2 4 5 -hexachlorobiphenyl (non-coplanar PB-type inducer) (HCBP), j8-naphthoflavone (BNF), polyaromatic hydrocarbons (PAH), — (not determined). 

Halwachs, S., Kneuer, C., and Honscha, W., 2007. Downregulation of the reduced folate carrier transport activity by phenobarbital-type cytochrome P450 inducers and protein kinase C activators. Biochimica et Biophysica Acta. 1768 1671-1679. 

Goldstein, J.A., P. Hickman, H. Bergaman, J.D. McKinney, and M.P Walker. 1977. Separation of pure polychlorinated biphenyl isomers into two types of inducers on the basis of induction of cytochrome P-450 or P-448. Chem.-Biol. Interact. 17 69-87. 

Lecoeur, S., Andre, C., and Beaune, P.H., Tienilic acid-induced autoimmune hepatitis Antiliver and-kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9, Mol. Pharmacol., 50,326, 1996. 

M.L. Avery, C.E. Meek, and K.L. Audus. The presence of inducible cytochrome P450 types 1A1 and 1A2 in the BeWo cell line. Placenta. 24 45-52 (2003). 

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