title: The inhibition effect of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin-induced aryl hydrocarbon receptor activation in human hepatoma cells with the treatment of cadmium chloride.
abstract: Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), considered as endocrine disruptors, tend to accumulate in fatty tissues. Dioxin-responsive element chemical activated luciferase gene expression assay (DRE-luciferase assay) has been recognized as a semi-quantitative method for screening dioxins for its fast and low-cost as compared with HRGC/HRMS. However, some problems with the bioassay, including specificity, detection variation resulted from different cleanup strategies, and uncertainty of false-negative or false-positive results, remain to be overcome. Cadmium is a prevalent environmental contaminant around the world. This study was aimed to examine the effects of cadmium on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of aryl hydrocarbon receptor (AhR)-mediated gene expression in human hepatoma cells (Huh7-DRE-Luc cells and Huh7 cells). Ethoxyresorufin-O-deethylase (EROD) and DRE-luciferase assay were employed to determine the enzyme activity of cytochrome P450 1A1 (CYP1A1) and activation of AhR, respectively. The results showed that Cd(2+) levels significantly inhibited the induction of TCDD-induced CYP1A1 and DRE luciferase activation in hepatoma cells. The 50% inhibited concentrations (IC(50)) of CdCl(2) were 0.414 microM (95% confidence interval (C.I.): 0.230-0.602 microM) in Huh7-DRE-Luc cells and 23.2 microM (95% C.I.: 21.7-25.4 microM) in Huh7 cells. Accordingly, prevention of interference with non-dioxin-like compounds in a DRE-luciferase assay is of great importance in an extensive cleanup procedure.
authors.affiliation: Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan.
authors.forename: How-Ran
authors.initials: HR
authors.lastname: Chao
authors.forename: Tsui-Chun
authors.initials: TC
authors.lastname: Tsou
authors.forename: Hung-Ta
authors.initials: HT
authors.lastname: Chen
authors.forename: Eddy Essen
authors.initials: EE
authors.lastname: Chang
authors.forename: Feng-Yuan
authors.initials: FY
authors.lastname: Tsai
authors.forename: Ding-Yan
authors.initials: DY
authors.lastname: Lin
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Chen
authors.forename: Ya-Fen
authors.initials: YF
authors.lastname: Wang
mesh_terms: D019256:Cadmium Chloride / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D052244:Endocrine Disruptors / Q000494:pharmacology; D004785:Environmental Pollutants; D006801:Humans; D020128:Inhibitory Concentration 50; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019256:Cadmium Chloride