title: Effects of o,p'-DDT on the 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible CYP1A1 expression in murine Hepa-1c1c7 cells.
abstract: Cultured mouse hepatoma Hepa-1c1c7 cells were treated with o,p'-DDT and/or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to assess the role of o,p'-DDT on CYP1A1 expression. o,p'-DDT alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, TCDD-inducible EROD activities were markedly reduced on concomitant treatment with TCDD and o,p'-DDT in a dose-dependent manner. Treatment with ICI 182.780, an estrogen-receptor antagonist, did not affect the suppressive effects of o,p'-DDT on TCDD-inducible EROD activity. TCDD-inducible CYP1A1 mRNA levels were markedly suppressed on treatment with TCDD and o,p'-DDT, and this was consistent with their effects on EROD activity. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and an electrophoretic mobility shift assay revealed that o,p'-DDT reduced the transformation of the aryl hydrocarbons (Ah) receptor to a form capable of specifically binding to the DRE sequence in the promoter region of the CYP1A1 gene. These results suggest that the downregulation of CYP1A1 gene expression by o,p'-DDT in Hepa-1c1c7 cells might be an antagonism of the DRE binding potential of the nuclear Ah receptor but is not mediated through the estradiol receptor.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju, South Korea. hgjeong@mail.chosun.ac.kr
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D003634:DDT / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology; D004785:Environmental Pollutants / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism; D020218:Response Elements; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004147:Dioxins; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; D003634:DDT; C016340:o,p'-DDT; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1