Radice Sonia, Chiesara Enzo, Fucile Serena, Marabini Laura
Department of Pharmacology, Chemotherapy and Medical Toxicology E. Trabucchi, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy.
Food Chem Toxicol. 2008 Jul;46(7):2561-7. doi: 10.1016/j.fct.2008.04.012. Epub 2008 Apr 14.
Polychlorinated biphenyls (PCBs) are ubiquitous, persistent environmental contaminants that can be a potential health hazard. In the present study we analyzed the potential estrogenic effect in MCF-7 cells of four biologically relevant PCB congeners, alone or in mixtures, present in dairy products, vegetable oil and fish: PCB101, PCB118, PCB138 and PCB153. The mixture of four PCB was tested at seven different concentrations. We investigated the ability of these PCBs, alone or mixed, to induce cell proliferation, and the level of estrogen-regulated protein pS2, in human MCF-7 breast cancer cells. PCB153 (35 microM) stimulated cell proliferation from 48 h up to day 6, PCB118 (40 microM) only at 48 h, but PCB101 (45 microM) and PCB138 (15 microM) applied to the cells for 6 days had no effect. In contrast, the various concentrations of mixtures significantly reduced cell proliferation at different times. No change in pS2 levels was seen after treatment with the PCBs alone or mixed. In exploring the mechanism of these events, we found that PCB153 induced mitogen-activated protein kinase (MAPK) ERK1/2 at 4, 8 and 12 h, while the antiproliferative effect seemed to be related to an apoptotic action beginning at 12 h and ending at 48 h. These findings indicate that these PCBs alone or mixed have no estrogenic effect in MCF-7 cells, although PCB153 induce an ERK1/2-mediated mitogenic effect. On the contrary the mixture of PCBs induces an antiproliferative effect, ascribable to an apoptotic action.
多氯联苯（PCBs）是普遍存在且持久的环境污染物，可能对健康构成潜在危害。在本研究中，我们分析了乳制品、植物油和鱼类中存在的四种具有生物学相关性的多氯联苯同系物（单独或混合存在），即PCB101、PCB118、PCB138和PCB153，对MCF-7细胞的潜在雌激素效应。对四种多氯联苯的混合物进行了七种不同浓度的测试。我们研究了这些多氯联苯单独或混合时诱导人MCF-7乳腺癌细胞增殖的能力以及雌激素调节蛋白pS2的水平。PCB153（35微摩尔）从48小时到第6天刺激细胞增殖，PCB118（40微摩尔）仅在48小时有刺激作用，但将PCB101（45微摩尔）和PCB138（15微摩尔）作用于细胞6天则无效果。相反，不同浓度的混合物在不同时间显著降低细胞增殖。单独或混合使用多氯联苯处理后，pS2水平未见变化。在探究这些事件的机制时，我们发现PCB153在4、8和12小时诱导丝裂原活化蛋白激酶（MAPK）ERK1/2，而抗增殖作用似乎与从12小时开始并在48小时结束的凋亡作用有关。这些发现表明，这些多氯联苯单独或混合在MCF-7细胞中没有雌激素效应，尽管PCB153诱导了ERK1/2介导的促有丝分裂效应。相反，多氯联苯混合物诱导了抗增殖效应，这可归因于凋亡作用。
