ESTROGENIC PESTICIDES - BINDING RELATIVE TO ESTRADIOL IN MCF-7 CELLS AND EFFECTS OF EXPOSURE DURING FETAL LIFE ON SUBSEQUENT TERRITORIAL BEHAVIOR IN MALE-MICE
ESTROGENIC PESTICIDES - BINDING RELATIVE TO ESTRADIOL IN MCF-7 CELLS AND EFFECTS OF EXPOSURE DURING FETAL LIFE ON SUBSEQUENT TERRITORIAL BEHAVIOR IN MALE-MICE
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DOI：
10.1016/0378-4274(95)03316-5
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发表时间：
1995-05-01
影响因子：
3.5
通讯作者：
WELSHONS, WV
中科院分区：
文献类型：
--
作者：
VOMSAAL, FS;NAGEL, SC;WELSHONS, WV
人类释放到环境中的许多化学物质能够通过与雌激素反应细胞中的雌激素受体结合来破坏内分泌系统的功能。在无血清培养基和100%血清中检测了o，p '-二氯二苯基三氯乙烷（DDT）和甲氧滴滴涕与雌二醇竞争结合MCF-7细胞中雌激素受体的能力（相对结合亲和力; RBA）;这被称为相对结合亲和力-血清修饰进入（RBA-SMA）试验。RBA的范围从o，p '-DDT的0.04%（相对于无血清培养基，其显示出对血清中细胞的增加的接触）到甲氧滴滴涕的0.004%（其未显示出对血清中细胞的增加的接触）。基于这些发现，这些农药，沿着与己烯雌酚（DES）作为阳性对照，从妊娠第11-17天喂给妊娠小鼠。当雄性后代成年后在新领域（领域行为）中检查尿液标记率时，尿液标记率在低剂量DES（相对于对照组）下显着增加，然后在产前给予最高剂量时显着下降。MCF-7细胞中的相对结合准确地预测了产生相同结果的o，p '-DDT和甲氧滴滴涕的剂量，为以下假设提供了支持：对行为的影响是通过与发育中大脑中的雌激素受体结合来介导的。
Numerous chemicals released into the environment by man are able to disrupt the functioning of the endocrine system by binding to estrogen receptors in estrogen-responsive cells. The ability of o,p'-dichlorodiphenyl trichloroethane (DDT) and methoxychlor to compete with estradiol for binding to estrogen receptors in MCF-7 cells (relative binding affinity; RBA) was examined in both serum-free medium and 100% serum; this is referred to as a relative binding affinity-serum modified access (RBA-SMA) assay. RBA's ranged from 0.04% for o,p'-DDT (which showed enhanced access to cells in serum relative to serum-free medium) to 0.004% for methoxychlor (which did not show enhanced access in serum). Based on these findings, these pesticides, along with diethylstilbestrol (DES) as a positive control, were fed to pregnant mice from days 11-17 of pregnancy. When the male offspring were examined in adulthood for their rate of urine marking in a novel territory (territorial behaviour), the rate of urine marking increased dramatically with low doses of DES (relative to controls) and then decreased significantly at the highest dose administered prenatally. Relative binding in MCF-7 cells accurately predicted the doses of o,p'-DDT and methoxychlor that produced the same results, providing support for the hypothesis that effects on behaviour were mediated by binding to estrogen receptors in the developing brain.