Effects of o,p'-DDT on the 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible CYP1A1 expression in murine Hepa-1c1c7 cells.
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.
Jeong
Hye Gwang
HG
Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju, South Korea. hgjeong@mail.chosun.ac.kr
Kim
Ji Young
JY
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
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