Jeong H G, Kim J Y, Choi C Y, You H J, Hahm K
Department of Pharmacy, Chosun University, 375 Seosuk-dong, Gong-ku, 501-759, Kwangju, South Korea.
Cancer Lett. 2001 Apr 10;165(1):95-101. doi: 10.1016/s0304-3835(01)00407-4.
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.
本研究调查了4-壬基酚（NP）对Hepa-1c1c7细胞培养物中CYP1A1表达的影响。单独使用NP不影响CYP1A1特异性7-乙氧基异吩恶唑酮-O-脱乙基酶（EROD）活性。相反，在同时用2,3,7,8-四氯二苯并对二恶英（TCDD）和NP处理时，TCDD诱导的EROD活性以剂量依赖的方式显著降低。用他莫昔芬（一种通过雌激素受体起作用的抗雌激素）处理，并不影响NP对TCDD诱导的EROD活性的抑制作用。在同时用TCDD和NP处理时，TCDD诱导的CYP1A1 mRNA水平显著受到抑制，这与其对EROD活性的影响一致。使用二恶英反应元件（DRE）连接的荧光素酶进行的瞬时转染试验和电泳迁移率变动分析表明，NP降低了芳烃（Ah）受体向能够特异性结合CYP1A1基因启动子DRE序列的形式的转化。这些结果表明，NP在Hepa-1c1c7细胞中对CYP1A1基因表达的下调可能是对核Ah受体DRE结合潜力的拮抗作用，但不是通过雌二醇受体介导的。
