title: Arsenic inhibits induction of cytochrome P450 1A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin in human hepatoma cells.
abstract: The aim of this study was to examine the arsenic effect on activation of aryl hydrocarbon receptor (AhR)-mediated gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in human hepatoma cells. The human hepatoma Huh7 cells were treated with sodium arsenite (NaAsO2) from 0.5 to 20 microM for 24 h. Our data revealed that NaAsO2 < or = 10 microM caused no significant cytotoxic effect on Huh7 cells (p>0.05). We also established a dioxin-responsive element (DRE)-mediated Chemical Activated LUciferase eXpression (CALUX) cell line, Huh7-DRE-Luc, by stable transfection of Huh7 with a DRE-driven firefly luciferase reporter plasmid (4xDRE-TATA-Luc). Treatments of Huh7-DRE-Luc and Huh7 with NaAsO2 attenuated the 2,3,7,8-TCDD-induced DRE-CALUX and cytochrome P450 1A1 (CYP1A1) activations, respectively, in a dose-dependent manner. We found that the calculated CALUX-toxic equivalent (TEQ) levels induced by cotreatment of NaAsO2 > or = 3.0 microM and 10 nM 2,3,7,8-TCDD were significantly lower than that induced by 2,3,7,8-TCDD alone (p<0.05). In the present study, we demonstrated that arsenic not only inhibited the TCDD-induced CYP1A1 activation but also interfered with DRE-CALUX bioassay in human hepatoma cells. Our finding also suggests that extensive cleanup of sample for removal of any possible interfering factor is critical to guarantee the accuracy of dioxin-TEQ levels using DRE-CALUX bioassay.
authors.affiliation: Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, 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: Lih-Ann
authors.initials: LA
authors.lastname: Li
authors.forename: Feng-Yuan
authors.initials: FY
authors.lastname: Tsai
authors.forename: Ya-Fen
authors.initials: YF
authors.lastname: Wang
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Tsai
authors.forename: Eddy Essen
authors.initials: EE
authors.lastname: Chang
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Miao
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Wu
authors.forename: Wen-Jhy
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D001149:Arsenates / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D004785:Environmental Pollutants / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D001149:Arsenates; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D000072317:Polychlorinated Dibenzodioxins; C009277:sodium arsenate; D019363:Cytochrome P-450 CYP1A1