TOXICANT INDUCED CHANGES IN UTERINE & CERVICAL EPITHELIA

多环芳烃(PAHs)，如苯并(A)芘 环境分布。工业化学品，如卤代芳烃 碳氢化合物也是广泛存在的环境污染物。2，3，7，8- 四氯二苯并对二恶英(TCDD)是其中最重要的成员 类，并且是研究它们的操作机制的有用原型。 公众关注的一个主要问题是这些化合物对 女性生殖道功能与胎儿发育。虽然 这些药物对生殖道的毒性已在动物身上得到证实。 模型，对它们的直接影响知之甚少 对人类女性生殖道功能的影响。 我们最近开发了人类子宫内膜和宫颈外细胞培养。 系统作为人类生殖道上皮细胞功能的模型。 这些细胞对生理上重要的性激素做出反应， 雌激素和黄体酮，以一种模仿体内反应的方式。 在目前的研究中，我们计划利用这些系统来研究这些影响 TCDD和PAHs对生殖道上皮细胞功能的影响。 具体地说，我们将：[1]检查TCDD、BP、奔驰(A)的影响 菲(BA)对子宫内膜上皮细胞的作用 子宫颈外上皮细胞分化的特异性研究 宫颈外细胞标记物(即，包皮蛋白和角蛋白mRNA和蛋白， 转谷氨酰胺酶、P450及相关酶和DNA修饰)，[2] 确定这些制剂是否会改变EE或ECEs细胞对性别的反应 通过调节各自受体的水平或亲和力来调节类固醇 和[3]确定药物新陈代谢的程度，从而产生毒性 根据细胞分化状态的不同，其效力也不同。 这些实验的最终目标是获得对 这些化合物在扰乱正常女性生殖方面可能起到的作用。

The polycyclic aromatic hydrocarbons (PAHs), such as benzo (a) pyrene environmental distribution. Industrial chemicals like halogenated aromatic hydrocarbons are also widespread environmental contaminants. 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) is the most important member of this class and is a useful prototype to investigate their mechanism of action. A major public concern is the potential effects of these compounds on female reproductive tract function and fetal development. Although reproductive tract toxicity by these agents has been demonstrated in animal models, very little knowledge is available regarding their direct effects on human female reproductive tract function. We have recently developed human endometrial and ectocervical cell culture systems as models for human reproductive tract epithlelial cell function. These cells respond to the physiologically important sex steroids, estradiol and progesterone, in a manner that mimics the in vivo response. In the present study we plan to utilize these systems to study the effects of TCDD and PAHs on reproductive tract epithelial cell function. Specifically, we will: [1] examine the effects of TCDD, BP, benz (a) anthracene (BA) upon endometrial epithelial cells (EE cell) and ectocervical epithelial cell (ECE cell) differentiation using specific ectocervical cell markers (i.e., involucrin and keratin mRNA and protein, transglutaminase, P450 and related enzymes and DNA modification), [2] determine whether these agents alter EE or ECE cell response to the sex steroids by regulating the levels or affinity of their respective receptors and [3] determine whether the extent of drug metabolism and thus toxic potency differs depending upon the differentiated state of the cells. The ultimate goal of these experiments is to gain new insights into the role that these compounds may play in upsetting normal female reproduction.