Strain differences in vaginal responses to the xenoestrogen bisphenol A.
Strain differences in vaginal responses to the xenoestrogen bisphenol A.
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DOI：
10.1289/ehp.00108243
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发表时间：
2000-03
影响因子：
10.4
通讯作者：
Bigsby RM
中科院分区：
文献类型：
--
作者：
Long X;Steinmetz R;Ben-Jonathan N;Caperell-Grant A;Young PC;Nephew KP;Bigsby RM
双酚A（BPA）是聚碳酸酯塑料和环氧树脂的单体成分;人类接触双酚A的来源是用某些塑料包装的食品中的沥滤物或环氧基牙科器具。BPA刺激Fischer 344（F344）大鼠的催乳素分泌，但不刺激Sprague-Dawley（S-D）大鼠。目前的研究是为了确定另一个经典的雌激素靶组织，大鼠阴道，响应双酚A的应变特异性的方式。在F344大鼠中，BPA增加了阴道上皮的DNA合成，中位有效剂量（艾德（50））为37.5 mg/kg体重;在S-D大鼠中，任何试验剂量均未刺激DNA合成。在两种品系的大鼠中，（3）H-BPA从血液中的清除遵循相同的时间过程，半衰期为90分钟。[（3）H]雌二醇结合的Scatchard分析显示，在阴道雌激素受体的浓度或亲和力方面没有品系差异。BPA增加了即刻早期基因c-fos的mRNA水平，在两种大鼠品系中具有相似的剂量反应曲线。因此，F344和S-D大鼠在阴道上皮细胞增殖水平上表现出对BPA敏感性的差异。然而，BPA的代谢清除率和导致增殖反应、受体-配体相互作用和诱导立即早期基因的早期事件没有显示出菌株差异。这些观察结果表明，中间效应的差异必须考虑到对异种雌激素的增殖反应的敏感性的差异。此外，这些结果表明，在试图测试外源性物质的雌激素效应时，需要谨慎选择合适的终点和动物模型。
Bisphenol A (BPA) is the monomer component of polycarbonate plastics and epoxy resins; human exposure derives from leachate in foodstuffs packaged in certain plastics or from epoxy-based dental appliances. BPA stimulates prolactin secretion in Fischer 344 (F344) rats but not in Sprague-Dawley (S-D) rats. The present studies were performed to determine if another classic estrogen target tissue, the rat vagina, responds to BPA in a strain-specific manner. In F344 rats BPA increased DNA synthesis in vaginal epithelium with a median effective dose (ED(50)) of 37.5 mg/kg body weight; DNA synthesis was not stimulated in S-D rats by any dose tested. Clearance of (3)H-BPA from blood followed the same time course in both strains of rats, with a half-life of 90 min. Scatchard analysis of [(3)H]estradiol binding showed no strain differences in concentration or affinity of the vaginal estrogen receptor. BPA increased the level of mRNA for the immediate early gene, c-fos, with similar dose-response curves in both rat strains. Thus, F344 and S-D rats exhibit differences in sensitivity to BPA at the level of cell proliferation in the vaginal epithelium. However, metabolic clearance of BPA and the early events that lead to the proliferative response, receptor-ligand interaction and induction of immediate early genes, show no strain differences. These observations suggest that differences in intermediate effects must account for the difference in sensitivity of the proliferative response to the xenoestrogen. Furthermore, these results point to the need for caution in choosing a suitable end point and animal model when seeking to test the estrogenic effects of xenobiotics.