title: Structure-dependent Ah receptor agonist activities of chlorinated biphenylenes.
abstract: Polychlorinated biphenylenes (PCBP) have been identified as combustion by-products that bind the aryl hydrocarbon receptor (AhR) and exhibit 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like activity. This study investigates the Ah-responsiveness of 2,3,6,7-tetrachlorobiphenylene (2,3,6,7-CBP), 2,3,6-CBP, 2,3-CBP and 2-CBP in breast cancer cells. MCF-7 or ZR-75 cells were treated with different concentrations (1-100 nM) of the compounds alone to determine their activity as inducers of CYP1A1 protein expression or luciferase activity in cells transfected with a construct (pDRE(3)) containing three tandem dioxin responsive elements (DREs) linked to a luciferase reporter gene. In both assays, the order of potency was 2,3,6,7-CBP>2,3,6-CBP>2,3-CBP approximately 2-CBP, and 2,3,6,7-CBP and TCDD were equipotent. Similar results were also observed in an antiestrogenic assay in MCF-7 cells, confirming the high AhR agonist activity of 2,3,6,7-CBP in breast cancer cells.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Khan
authors.forename: Alex
authors.initials: A
authors.lastname: Konstantinov
authors.forename: Brock
authors.initials: B
authors.lastname: Chittim
authors.forename: Alan
authors.initials: A
authors.lastname: McAlees
authors.forename: Brian
authors.initials: B
authors.lastname: Yeo
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014162:Transfection
chemical_list: C516412:2,3,6,7-tetrachlorobiphenylene; C516411:2,3,6-trichlorobiphenylene; C516410:2,3-dichlorobiphenylene; D047628:Estrogen Receptor alpha; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1