Down-regulation of murine Cyp1a-1 in mouse hepatoma Hepa-1c1c7 cells by bisphenol A.
Cultured mouse hepatoma Hepa-1c1c7 cells were treated with either bisphenol A or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or in combination to assess the role of bisphenol A in the process of Cyp1a-1 induction. Treatment of Hepa-1c1c7 cultures with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) induced Cyp1a-1, as determined by analysis of 7-ethoxyresorufin O-deethylase (EROD) activities. Bisphenol A alone did not affect the activity of Cyp1a-1-specific EROD; in contrast, TCDD-induced EROD activities were markedly reduced in the concomitant treatment of TCDD and bisphenol A in a dose-dependent manner. Treatment with tamoxifen, an antiestrogen that acts through the estrogen receptor, did not affect the suppressive effects of bisphenol A on TCDD-induced EROD activity. TCDD-induced Cyp1a-1 mRNA levels were markedly suppressed in the concomitant treatment of TCDD and bisphenol A consistent with their effects on EROD activity. Transient transfection assay using dioxin-response element (DRE)-linked luciferase revealed that bisphenol A reduced transformation of the aryl hydrocarbons (Ah) receptor to a form capable of specifically binding to the DRE sequence in the promoter of the Cyp1a-1 gene. These results suggest the down-regulation of the Cyp1a-1 gene expression by bisphenol A in Hepa-1c1c7 cells might be antagonism of the DRE binding potential of nuclear Ah receptor but not mediated through estradiol receptor.
Jeong
H G
HG
Department of Pharmacy, Chosun University, Kwangju, 501-759, South Korea. hgjeong@mail.chosun.ac.kr
Kimand
J Y
JY
Choi
C Y
CY
D000818:Animals; D001559:Benzhydryl Compounds; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D015536:Down-Regulation; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D019363:Cytochrome P-450 CYP1A1; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds