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Monoclonal antibodies have been successfully isolated which are isozyme-specific for cytochrome P450p (3A1) or P4501 (3A2), two members of the steroid-inducible cytochrome P450 subfamily exhibiting 89% amino acid sequence homology, and these antibodies show less than 5% cross-reaction with 11 other cytochromes P450 (P450a-P450k). A library of 28 purified(More)
A multitude of xenobiotics have been demonstrated to co-induce either cytochromes P-450c and P-450d or cytochromes P-450b and P-450e in rat hepatic microsomes. Recently, the compounds 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) and 3-methoxy-4-aminoazobenzene (3-MeO-AAB) have been suggested as selective inducers of cytochrome P-450b (Eur. J. Biochem. 151:67(More)
Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent hepatocarcinogen, and 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PCDD) on liver and kidney DNA of female Sprague-Dawley rats were investigated by 32P-post-labeling assay. The compounds were administered by gavage [1 microgram/kg/week in corn oil (5 ml/kg)] to the animals for up to 6 months. No(More)
RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A,(More)
The purpose of this study was to characterize hepatic cytochrome P450 induction in the dog by phenobarbital, beta-naphthoflavone, dexamethasone, and isoniazid using catalytic activities and Western blots with antibodies prepared against rat cytochrome P450 isozymes. Male beagle dogs were treated with phenobarbital (10 mg/kg for 2 days and 30 mg/kg for the(More)
The effects of treatment with phenobarbital, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), pregnenolone-16 alpha-carbonitrile (PCN), 3-methylcholanthrene (3-MC) and isosafrole on the hepatic microsomal formation of nine monohydroxy metabolites of testosterone and the O-dealkylation of the ethyl and pentyl ethers of resourfin were evaluated in adult(More)
1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) resembles phenobarbital (PB) in its mode of induction of the hepatic drug-metabolizing enzymes in mice. The structural features of this molecule include: a linear tricyclic aromatic ether ring system, an internal 1,4-disubstituted benzene ring and two 3,5-dichloropyridyloxy substituents. Ten analogs of(More)
p,p'-DDE, phenobarbital, dieldrin heptachlor, chlordane and toxaphene induced rat liver microsomes exhibited increased formation of the 4,5-dihydrodiol, 3,6-quinone, 9- and 3-hydroxymetabolites of benzo[a]pyrene and the latter three compounds also induced an increase in the rate of formation of the 9,10-dihydrodiol metabolite. Lindane was inactive as an(More)
The contribution of individual cytochrome P-450 isozymes in the hydroxylation of the centrally acting skeletal muscle relaxant chlorzoxazone was determined in rat liver microsomes. The hydroxylation rate of chlorzoxazone was found to be 50% greater in male than female microsomes. Kinetic studies using control male microsomes showed that chlorzoxazone(More)
Preclinical safety studies with the leukotriene D4 antagonist RG 12525 were conducted by the oral route in mice, rats, and monkeys. Oral administration of RG 12525 was repeated daily in studies up to 6 months in duration. RG 12525 was shown to have limited high-dose toxicity after repeated oral administration. The effects of RG 12525 were strongly dependent(More)