Antiestrogenicity of environmental polycyclic aromatic hydrocarbons in human breast cancer cells
Antiestrogenicity of environmental polycyclic aromatic hydrocarbons in human breast cancer cells
复制标题
DOI：
10.1016/s0300-483x(99)00018-9
复制
发表时间：
1999-04-15
期刊：
影响因子：
4.5
通讯作者：
Gierthy, JF
中科院分区：
文献类型：
--
作者：
Arcaro, KF;O'Keefe, PW;Gierthy, JF
14个多环芳烃（PAHs）的总浓度被确定为3400倍以上的沉积物样品从一个工业网站的圣劳伦斯河（SLR），纽约州，比在沉积物样品从一个非工业网站的Kinderhook河（KC），纽约州。多环芳烃馏分提取物的两个环境样品和两个重建的混合物，以及14个单独的多环芳烃的毒性，雌激素和抗雌激素活性进行了检查，使用MCF-7焦点，重组人雌激素受体（ER）结合，全细胞ER结合，和17 β-雌二醇（E-2）代谢试验。从KC和SLR PAH馏分抗雌激素，它们显着抑制了由1 nM E-2在MCF-7乳腺癌细胞中引起的病灶的形成。14种多环芳烃中的8种，以及重组的混合物也具有抗雌激素活性。从全细胞ER结合试验和E-2代谢的放射性分析的结果表明，在KC和SLR环境样品中检测到的多环芳烃诱导抗雌激素反应，在代谢完整的人乳腺癌细胞通过至少两种机制：一个涉及竞争的ER由PAH代谢物和其他涉及耗尽E-2通过诱导代谢。出版社：Elsevier Science爱尔兰有限公司
The total concentration of 14 polycyclic aromatic hydrocarbons (PAHs) was determined to be 3400-fold greater in a sediment sample from an industrial site on the St. Lawrence River (SLR), NY, than in a sediment sample from a non-industrial site on the Kinderhook Creek (KC), NY. PAH fractions from extracts of the two environmental samples and two reconstituted mixtures as well as the 14 individual PAHs were examined for their toxic, estrogenic, and antiestrogenic activities using MCF-7 focus, recombinant human estrogen receptor (ER) binding, whole-cell ER binding, and 17 beta-estradiol (E-2) metabolism assays. PAH fractions from the KC and SLR were antiestrogenic; they significantly inhibited the formation of foci elicited in MCF-7 breast cancer cells by 1 nM E-2. Eight of the 14 individual PAHs, and the reconstituted mixtures were also antiestrogenic. Results from the whole-cell ER binding assay and the radiometric analysis of E-2 metabolism indicate that the PAHs detected in the KC and the SLR environmental samples induce antiestrogenic responses in metabolically intact human breast cancer cells through at least two mechanisms: one involving competition for the ER by a PAH metabolite and the other involving depletion of E-2 through induction of metabolism. Published by Elsevier Science Ireland Ltd.