Suppression of CYP1A1 expression by 4-nonylphenol in murine Hepa-1c1c7 cells

被引:16
作者
Jeong, HG
Kim, JY
Choi, CY
You, HJ
Hahm, KS
机构
[1] Chosun Univ, Dept Pharm, Gong Ku, Kwangju 501759, South Korea
[2] Chosun Univ, Res Ctr Proteineous Mat, Kwangju 501759, South Korea
关键词
4-nonylphenol; CYP1A1; suppression;
D O I
10.1016/S0304-3835(01)00407-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:95 / 101
页数:7
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