Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.
Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.
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DOI：
10.2131/jts.26.111
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发表时间：
2001-08-01
期刊：
影响因子：
--
通讯作者：
Park, K L
中科院分区：
文献类型：
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作者：
Kim, H S;Han, S Y;Park, K L
双酚 A 的潜在雌激素活性在体外（电子筛选和雌激素受体竞争性结合生物测定）和体内（子宫营养测定）进行了研究。使用连续 3 天皮下注射双酚 A（1、5、10、50 和 100 毫克/公斤/天）、E2（0.3 微克/公斤）和 DES（0.3 微克/公斤）的成熟卵巢切除 Sprague-Dawley 雌性大鼠来评估子宫营养反应。在MCF-7细胞增殖测定中，E2和DES用作阳性雌激素，在1.0 nM时诱导MCF-7细胞最大增殖，而BPA在0.1 µM的较高水平下轻微诱导MCF-7细胞增殖，在10 µM时诱导最大增殖。在竞争性结合测定中，E2 和 DES 可抑制 17 β-[3H]雌二醇与大鼠子宫 ER 的结合，IC50 分别为 1.0 nM 和 0.5 nM。然而，BPA 的 IC50 为 5 µM，比 E2 和 DES 的 IC50 高约 5,000 或 10,000 倍。在子宫营养测定中，OVX Sprague-Dawley 大鼠中 BPA 剂量为 100 mg/kg/天时，子宫（湿的和吸干的）和阴道重量显着增加。这些研究表明，BPA 在所有实验系统中均表现出较弱的雌激素活性，因此应控制其从环氧树脂或聚碳酸酯产品中的迁移不超过对人类的安全水平。
The potential estrogenic activities of bisphenol-A were investigated in vitro (E-screen and estrogen receptor competitive binding bioassays) and in vivo (uterotrophic assay). Uterotrophic responses were evaluated using mature ovariectomized Sprague-Dawley female rats treated subcutaneously with bisphenol A (1, 5, 10, 50, and 100 mg/kg/day), E2 (0.3 microgram/kg), and DES (0.3 microgram/kg) for 3 consecutive days. In a MCF-7 cell proliferation assay, E2 and DES used as positive estrogens induced maximum proliferation of MCF-7 cells at 1.0 nM, whereas BPA slightly induced MCF-7 cell proliferation at a higher level of 0.1 microM and maximum proliferation at 10 microM. In a competitive binding assay, E2 and DES showed inhibition of 17 beta-[3H]estradiol binding to the rat uterus ER with an IC50 of 1.0 nM and 0.5 nM, respectively. However, BPA had an IC50 of 5 microM, which was approximately 5,000 or 10,000-fold greater than the IC50 of E2 and DES. In uterotrophic assays, uterus (wet and blotted) and vagina weights were significantly increased at the dose of BPA 100 mg/kg/day in OVX Sprague-Dawley rats. These studies demonstrate that BPA exhibits weak estrogenic activity in all experimental systems, and thus its migration from epoxy resins or polycarbonate products should be controlled not to exceed a safety levels for humans.