Effects of the environmental oestrogens bisphenol A, tetrachlorobisphenol A, tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4′-dihydroxybiphenyl on oestrogen receptor binding, cell proliferation and regulation of oestrogen sensitive proteins in the human breast cancer cell line MCF-7
Effects of the environmental oestrogens bisphenol A, tetrachlorobisphenol A, tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4′-dihydroxybiphenyl on oestrogen receptor binding, cell proliferation and regulation of oestrogen sensitive proteins in the human breast cancer cell line MCF-7
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DOI：
10.1034/j.1600-0773.2003.920408.x
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发表时间：
2003-04-01
期刊：
影响因子：
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通讯作者：
Hongslo, JK
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文献类型：
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作者：
Olsen, CM;Meussen-Elholm, ETM;Hongslo, JK
双酚A广泛用于制造环氧树脂和聚碳酸酯塑料，而几种溴化和氯化类似物在塑料工业中被用作阻燃剂和中间体。由于这些化学品之间的结构关系和高产量，我们想用MCF-7细胞中的几个端点来表征和比较它们潜在的雌激素样效能：诱导pS2蛋白和孕酮受体，降低雌激素受体水平，刺激细胞生长。双酚A、四氯双酚A和四溴双酚A、4-羟基联苯和4,4′-二羟基联苯在MCF-7细胞中均表现出雌激素样特性。测试的化学物质与从MCF-7细胞中分离出来的雌激素受体有亲和力，尽管它们的EC50比17 -雌二醇的EC50高1000到8万倍。双酚A和4-羟基联苯诱导MCF-7细胞生长，且最高浓度诱导的反应明显超过17 -雌二醇诱导的细胞生长。其他被测试的化学物质诱导的细胞生长不到17 -雌二醇最大刺激的50%。双酚A、4-羟基联苯、四溴双酚A和四氯双酚A均能提高雌激素调节蛋白、孕酮受体和pS2的水平，而4,4′-二羟基联苯则无此作用。双酚A是唯一一种在降低MCF-7细胞内细胞内雌激素受体水平的能力上明显模仿17 -雌二醇的化学物质。通过测量几个雌激素依赖的终点，似乎一些异种雌激素引起不平衡的雌激素反应。它们在一个参数中模仿17 - β -雌激素的能力和效力不一定伴随着另一个与雌激素相关的参数的类似效果。
Bisphenol A is extensively used in the manufacturing of epoxy resins and polycarbonate plastics, whereas several brominated and chlorinated analogues are used as flame retardants and intermediates in the plastic industry Due to the structural relationship between these chemicals and the high production volumes, we wanted to characterize and compare their potential oestrogen-like potency using several end-points in MCF-7 cells: induction of pS2 protein and progesterone receptor, reduction of oestrogen receptor level, and stimulation of cell growth. Bisphenol A, tetrachloro- and tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4'-dihydroxybiphenyl all showed oestrogen-like properties in MCF-7 cells. The chemicals tested had affinity to the oestrogen receptor isolated from MCF-7 cells, although their EC50S were 1,000 to 80,000 times higher than the EC50 of 17beta-oestradiol. Bisphenol A and 4-hydroxybiphenyl induced cell growth in MCF-7 cells, and the highest test concentrations induced responses, apparently exceeding the cell growth induced by 17beta-oestradiol. The other chemicals tested induced less than 50% of the maximum 17beta-oestradiol-stimulated cell growth. Bisphenol A, 4-hydroxybiphenyl, tetrabromobisphenol A and tetrachlorobisphenol A all increased the level of the oestrogen-regulated proteins, progesterone receptor and pS2, whereas 4,4'-dihydroxybiphenyl showed no such effect. Bisphenol A was the only chemical tested that clearly mimicked 17beta-oestradiol in its ability to reduce the level of cytosolic oestrogen receptors in MCF-7 cells. By measuring several oestrogen-dependent endpoints it seems that some xeno-oestrogens cause an imbalanced oestrogen-response. Their ability and potency in mimicking 17beta-oestrogen in one parameter is not necessarily accompanied by a similar effect in another oestrogen-linked parameter.