Suppression of CYP1A1 expression by 4-nonylphenol in murine Hepa-1c1c7 cells.
This study investigated the effects that 4-nonylphenol (NP) has on CYP1A1 expression in Hepa-1c1c7 cell cultures. NP alone did not affect CYP1A1-specific 7-ethoxyresorufin-O-deethylase (EROD) activity. In contrast, the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and NP in a dose-dependent manner. Treatment with tamoxifen, an anti-estrogen that acts through the estrogen receptor, did not affect the suppressive effects that NP has on TCDD-inducible EROD activity. The TCDD-inducible CYP1A1 mRNA levels were markedly suppressed upon concomitant treatment with TCDD and NP that is 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 NP reduced the transformation of the aryl hydrocarbon (Ah) receptor to a form capable of binding specifically to the DRE sequence of the CYP1A1 gene promoter. These results suggest that the down-regulation of CYP1A1 gene expression by NP 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.
Department of Pharmacy, Chosun University, 375 Seosuk-dong, Gong-ku, 501-759, Kwangju, South Korea. hgjeong@mail.chosun.ac.kr
H G
HG
Jeong
J Y
JY
Kim
C Y
CY
Choi
H J
HJ
You
K
K
Hahm
D000818:Animals; D006528:Carcinoma, Hepatocellular; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions; D004794:Enzyme Repression / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D008175:Lung Neoplasms; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000502:physiology; D013723:Teratogens / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010636:Phenols; D000072317:Polychlorinated Dibenzodioxins; D011960:Receptors, Estrogen; D013723:Teratogens; D019363:Cytochrome P-450 CYP1A1; C041594:4-nonylphenol