title: Binding of chlorinated benzidines to the rat hepatic aromatic hydrocarbon receptor.
abstract: The binding of benzidine, 3,3'-dichlorobenzidine (3,3'-Cl2BZ), and the asymmetrically-substituted chlorinated benzidines 3,5-dichlorobenzidine (3,5-Cl2BZ) and 3,5,3'-trichlorobenzidine (Cl3BZ) to the rat hepatic cytosolic aromatic hydrocarbon (Ah) receptor was measured, in order to assess the mechanism of P-450I induction by 3,3'-Cl2BZ. Cl3BZ is the most mutagenic benzidine derivative in the Ames assay. Binding affinity to the Ah receptor protein was determined by displacement of labelled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from the receptor, measured with the sucrose density gradient centrifugation technique. The rank order of affinities and the apparent inhibitor constants were: Cl3BZ (4 microM) greater than 3,5-Cl2BZ (8.4 microM) greater than 3,3'-Cl2BZ (10 microM). Benzidine did not displace TCDD from the receptor protein. 4-Aminobiphenyl a structural link between the benzidine and biphenyl series competed weakly with TCDD. The 50% inhibition concentration was about 150 microM. The results are consistent with the hypothesis that the induction of P-450 enzymes by 3,3'-Cl2BZ in vivo is mediated by the Ah receptor.
authors.affiliation: Institute of Toxicology and Pharmacology, University of Würzburg, F.R.G.
authors.forename: P
authors.initials: P
authors.lastname: Cikryt
authors.forename: P D
authors.initials: PD
authors.lastname: Josephy
mesh_terms: D015101:3,3'-Dichlorobenzidine / Q000378:metabolism / Q000494:pharmacology / Q000031:analogs & derivatives; D000818:Animals; D001560:Benzidines / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D002499:Centrifugation, Density Gradient; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D001560:Benzidines; D000072317:Polychlorinated Dibenzodioxins; D011956:Receptors, Cell Surface; D015101:3,3'-Dichlorobenzidine; C061843:3,5-dichlorobenzidine; C061844:3,3',5-trichlorobenzidine; D003577:Cytochrome P-450 Enzyme System