Safe S, Connor K, Gaido K
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843-4466, USA.
Toxicol Lett. 1998 Dec 28;102-103:665-70. doi: 10.1016/s0378-4274(98)00283-5.
Research in our laboratories has focused on development of a battery of in vivo and in vitro bioassays for determining estrogenic activity and potency of different classes of natural and synthetic industrial-derived estrogenic compounds (xenoestrogens) including food/beverage extracts, phytoestrogens, phenolic compounds, organochlorine pesticides and pollutants. For many of the weak estrogenic compounds, their activity as estrogen receptor (ER) agonists or antagonists is dependent on the gene/gene promoter, cell context and expression of ER(alpha) or ER(beta) isoform. For example, extracts of red wine, bound to the ER, exhibited estrogenic activity in T47D, MCF-7 (breast) and Hep G2 (liver) human cancer cell lines, whereas reconstituted organochlorine pesticide residues found in food were active only in Hep G2 cells that transiently expressed ER(alpha) or ER(beta). The relative potencies of red wine extracts versus reconstituted organochlorine pesticides were assay-dependent; however, estrogen equivalent daily intakes from a glass of red wine (approximately 0.5-2 microg estrogen equivalents/day) were at least 10(3) higher than observed for the reconstituted organochlorine pesticide mixtures. Risk assessment of xenoestrogens and other synthetic chemicals which modulate endocrine responses must take into account high dietary levels of natural products in food, drugs and health food store extracts which also modulate endocrine responses.
我们实验室的研究重点是开发一系列体内和体外生物测定方法，以确定不同类别的天然和合成工业来源雌激素化合物（外源性雌激素）的雌激素活性和效力，这些化合物包括食品/饮料提取物、植物雌激素、酚类化合物、有机氯农药和污染物。对于许多弱雌激素化合物而言，它们作为雌激素受体（ER）激动剂或拮抗剂的活性取决于基因/基因启动子、细胞环境以及ER（α）或ER（β）亚型的表达。例如，与ER结合的红酒提取物在T47D、MCF - 7（乳腺）和Hep G2（肝脏）人癌细胞系中表现出雌激素活性，而食品中发现的重构有机氯农药残留仅在瞬时表达ER（α）或ER（β）的Hep G2细胞中具有活性。红酒提取物与重构有机氯农药的相对效力取决于测定方法；然而，一杯红酒的雌激素当量每日摄入量（约0.5 - 2微克雌激素当量/天）比重构有机氯农药混合物的摄入量至少高10³ 倍。对外源性雌激素和其他调节内分泌反应的合成化学品进行风险评估时，必须考虑到食品、药物和保健食品店提取物中高含量的天然产物，这些天然产物也会调节内分泌反应。
