Bonefeld-Jørgensen E C, Andersen H R, Rasmussen T H, Vinggaard A M
Unit of Environmental Biotechnology, Department of Environmental and Occupational Medicine, University of Aarhus, Building 260, Vennelyst Boulevard 6, DK-8000, Aarhus, Denmark.
Toxicology. 2001 Feb 14;158(3):141-53. doi: 10.1016/s0300-483x(00)00368-1.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent contaminants giving rise to potential health hazard. Some PCBs exert dioxin-like activities mediated through the aryl hydrocarbon receptor. Although reports on interaction with other nuclear receptors are sparce, some congeners are hypothesized to possess endocrine disruptive potential. Here we present evidence that the three PCBs most abundant in biological extracts, 2,2',3'4,4',5-hexachlorobiphenyl (PCB#138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB#153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB#180) have pleiotropic effects on the estrogen- and androgen-receptor. In MCF-7 cells a slightly increased cell proliferation was observed at low concentrations (1-10 nM) in cells co-treated with 0.01 nM 17beta-Estradiol, whereas the compounds inhibited cell growth significantly at 1 and 10 microM. In reporter gene (ERE-tk-CAT) analysis the three congeners exhibited a significantly estrogen receptor-ligand mediated decrease of the chloramphenicol transferase activity in both control and 10 nM 17beta-estradiol induced MCF-7 cells. In addition, PCB#138 elicited a dose-dependent antagonistic effect on androgen receptor activity in transiently co-transfected Chinese Hamster Ovary cells with an IC(50), of 6.2 microM. In summary, this study indicate that the di-ortho, multiple-chloro substituted biphenyls, PCB#138, PCB#153 and PCB#180, can compete with the binding of the natural ligand to two nuclear receptors and thus possess the ability to interfere with sexual hormone regulated processes.
多氯联苯（PCBs）是普遍存在的环境持久性污染物，会对健康造成潜在危害。一些多氯联苯具有通过芳烃受体介导的二噁英样活性。尽管关于其与其他核受体相互作用的报道很少，但一些同系物被推测具有内分泌干扰潜力。在此，我们提供证据表明，生物提取物中含量最高的三种多氯联苯，即2,2',3',4,4',5-六氯联苯（PCB#138）、2,2',4,4',5,5'-六氯联苯（PCB#153）和2,2',3,4,4',5,5'-七氯联苯（PCB#180），对雌激素受体和雄激素受体具有多效性作用。在MCF-7细胞中，与0.01 nM 17β-雌二醇共同处理的细胞在低浓度（1 - 10 nM）时观察到细胞增殖略有增加，而这些化合物在1和10 μM时显著抑制细胞生长。在报告基因（ERE-tk-CAT）分析中，这三种同系物在对照细胞和10 nM 17β-雌二醇诱导的MCF-7细胞中均表现出雌激素受体配体介导的氯霉素转移酶活性显著降低。此外，PCB#138在瞬时共转染的中国仓鼠卵巢细胞中对雄激素受体活性产生剂量依赖性拮抗作用，IC(50)为6.2 μM。总之，本研究表明，二邻位、多氯取代的联苯PCB#138、PCB#153和PCB#180能够与天然配体竞争结合两种核受体，因此具有干扰性激素调节过程的能力。
