Estradiol enhances and estriol inhibits the expression of CYP1A1 induced by 2,3,7,8-tetrachlorodibenzo- p-dioxin in a mouse ovarian cancer cell line

• Published in: Toxicology (Amsterdam) Vol. 176; no. 3; pp. 229 - 243
• Main Authors: Son, Deok-Soo, Roby, Katherine F, Rozman, Karl K, Terranova, Paul F
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.07.2002; Amsterdam Elsevier Science
• Subjects: Animals; Biological and medical sciences; Blotting, Northern; Blotting, Western; Cell Division - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; CYP1A1; Cytochrome P-450 CYP1A1 - antagonists & inhibitors; Cytochrome P-450 CYP1A1 - biosynthesis; Dioxins - pharmacology; DNA - biosynthesis; DNA - genetics; Environmental Pollutants - pharmacology; Enzyme Induction - drug effects; Epithelial Cells - drug effects; Epithelial Cells - enzymology; EROD; Estradiol - pharmacology; Estriol - pharmacology; Estrogens; Female; Fluorescent Antibody Technique; Genetic Vectors; Indicators and Reagents; Luciferases - biosynthesis; Medical sciences; Mice; Ovarian cancer; Ovarian Neoplasms - enzymology; Polychlorinated Dibenzodioxins - antagonists & inhibitors; Polychlorinated Dibenzodioxins - pharmacology; Receptors, Steroid - drug effects; Reverse Transcriptase Polymerase Chain Reaction; Toxicology; Tumor Cells, Cultured; Various organic compounds; CYP1A1; EROD; Estrogens; Ovarian cancer; Enzyme inducer; Isozyme; Toxicity; Cytochrome P450; Interaction; Tumor promotor; Rodentia; Endocrine disruptor; Malignant tumor; Gene expression; Estradiol; In vitro; Female genital diseases; Carcinogen; Ovary; Vertebrata; Mammalia; Mouse; Estrone; Tumor cell
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(02)00162-2

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is a ubiquitous pollutant and promoter of carcinogenesis. This study investigated the interaction between TCDD and different estrogens in a cancer cell line (ID8) derived from mouse ovarian epithelium. TCDD-induced ethoxyresorufin- O-deethylase (EROD) activity and cytochrome P4501A1 (CYP1A1) expression in a dose- and time-dependent manner. Estrogen receptor (ER) α mRNAs were constitutively expressed, but ERβ and progesterone receptor (PR) mRNAs were not expressed. Induction of EROD by TCDD was completely inhibited by a α-naphthoflavone and phenanthroline, two aryl hydrocarbon receptor (AhR) antagonists. Progesterone and gonadotropins (FSH and LH) had no effect on the induction of EROD by TCDD. Congeners of 17β-estradiol (E2) increased the induction of EROD activity by TCDD dose-dependently in the relative potency order: estrone (El)>E2⩾4-hydroxyestradiol (4OHE2)⩾2-hydroxyestradiol (2OHE2). In contrast, estriol (E3) decreased EROD activity induced by TCDD. E2 increased TCDD-induced CYP1A1 protein and mRNA whereas E3 decreased both the protein and mRNA. E2 did not alter luciferase activity induced by TCDD in cells transfected with a luciferase reporter containing dioxin response elements (DRE) or a CYP1A1 promoter. In contrast, E3 dose-dependently decreased the luciferase activity. A pure anti-estrogen (ICI 182 780) inhibited the interaction between E2 and TCDD but did not block E3's effect on EROD activity. These results indicate that E2 may affect TCDD-induced CYP1A1 expression by a mechanism different from E3 in ID8 cells. It appears that the potentiation of E2 in the induction of CYP1A1 by TCDD occurs by a mechanism involving ERα since a specific ER antagonist blocked the potentiation. The inhibitory effect of E3 may be due to a rapid direct effect on EROD and a later suppression of CYP1A1 expression.