Wade M G, Desaulniers D, Leingartner K, Foster W G
Reproductive Toxicology Section, Health Canada, Ottawa, Ontario, Canada.
Reprod Toxicol. 1997 Nov-Dec;11(6):791-8. doi: 10.1016/s0890-6238(97)00062-2.
There is growing concern that estrogenic chemicals, both natural and human-made, may be causing a variety of reproductive disorders in wildlife and human populations. Recent in vitro data suggest that the interaction between some weakly estrogenic organochlorines, dieldrin, endosulfan, toxaphene, and chlordane, causes a synergistic increase in their estrogenic potency, an effect due to joint action on estrogen receptors (ER). As these studies were conducted using models of estrogen action derived from cells that are not physiologically controlled by estrogens, the relevance of these findings to human health are not clear. The present studies were conducted to examine the interaction between endosulfan and dieldrin in the activation of ER in or extracted from mammalian cells. Endosulfan and dieldrin showed no synergism in displacing 3H-E2 from rat uterine ER or in inducing the proliferation of MCF-7 breast cancer cells, an estrogen-dependent response. Furthermore, endosulfan (0.1 mg per animal per d) or dieldrin (0.1 mg), alone or in combination, injected intraperitoneally daily for 3 d, did not stimulate any uterotrophic activity nor had any effect on pituitary prolactin or other endocrine-related endpoints in immature female rats. These studies demonstrate that these weakly estrogenic compounds do not interact in a synergistic fashion in binding to ER or in activating ER-dependent responses in mammalian tissues or cells. Thus, these results suggest that coexposure to these weakly estrogenic environmental contaminants likely will not cause human reproductive toxicity related to estrogen action.
人们越来越担心，无论是天然的还是人造的雌激素类化学物质，可能正在导致野生动物和人类群体出现各种生殖紊乱。最近的体外数据表明，一些弱雌激素性有机氯化合物（狄氏剂、硫丹、毒杀芬和氯丹）之间的相互作用会导致它们的雌激素效力协同增加，这种效应是由于它们对雌激素受体（ER）的联合作用。由于这些研究是使用并非由雌激素进行生理控制的细胞所衍生的雌激素作用模型进行的，因此这些发现与人类健康的相关性尚不清楚。本研究旨在检测硫丹和狄氏剂在激活哺乳动物细胞中或从哺乳动物细胞中提取的ER方面的相互作用。硫丹和狄氏剂在从大鼠子宫ER中置换3H-E2或诱导MCF-7乳腺癌细胞增殖（一种雌激素依赖性反应）方面均未显示出协同作用。此外，硫丹（每只动物每天0.1毫克）或狄氏剂（0.1毫克）单独或联合腹腔内注射，每天一次，连续3天，对未成熟雌性大鼠既未刺激任何子宫营养活性，也未对垂体催乳素或其他内分泌相关指标产生任何影响。这些研究表明，这些弱雌激素性化合物在与ER结合或激活哺乳动物组织或细胞中的ER依赖性反应方面不会以协同方式相互作用。因此，这些结果表明，共同接触这些弱雌激素性环境污染物可能不会导致与雌激素作用相关的人类生殖毒性。
