BIOVAILABILITY OF SUPERFUND CHEMICALS

超级基金优先有机化学品可能在以下时间进入人类食物链 有很多条路线。在这些化学物质渗入水体的区域， 这些化学物质可能会被栖息的鱼类和贝类摄取，它们可能 反过来又被人类吃掉。污染农作物和牲畜 超级基金化学品也是可能的。因为对健康的不利影响 超级基金的化学品是剂量依赖的，摄取量 被系统吸收的材料通常是最重要的 参数来确定风险。这个项目试图了解一些 影响超级基金化学品生物利用度的因素， 包括肠道生物转化和动物的慢性暴露 到其他超级基金化学品，如氯化平面多环 化合物，是阿司匹林受体激动剂。除了诱导细胞色素P1A1外， AH受体激动剂有许多其他的生化和生理作用 效果。调查人员提议检验两个啊的假设 在超级基金网站发现的受体激动剂，即2，3，7，8- 四氯二苯并对二恶英和3，3‘，4，4’-四氯联苯 (三氯苯)引起生理和结构组成的变化 影响肠道生物利用度的肠道细胞 亲脂性化学物质的生物转化。这些人提出的问题 假说将在体内、原位和体外进行研究， 包括分子生物学，以鲶鱼为基础的技术 主要动物模型。第一个具体目标是检查 放射性标记TCB和TCB的肠道生物转化和生物利用度 2，2‘，4，4’，5，5‘-六氯联苯及氯化溶剂 三氯乙烯对照和TCDD或TCB诱导的鲶鱼。第二 具体目标与吸收机制有关。尽管它被广泛地 认为亲脂性外源物质完全被被动吸收 扩散，有来自以前研究的证据表明，其他媒介 载体介导的过程调节吸收。我们建议调查 精选蛋白、P-糖蛋白和谷胱甘肽-S的表达 转移酶，可能受AH受体激动剂的影响并参与 在对照组和对照组肠道中的亲脂性外源物质的转运 诱导鱼。这些研究将提供对这一过程的洞察 影响重要的超级基金化学品的饮食生物利用度。

Superfund priority organic chemicals may enter the human food chain by many routes. In areas where these chemicals leach into bodies of water, the chemicals may be taken up by resident fish and shellfish, which may in turn be eaten by humans. Contamination of crops and livestock by superfund chemicals is also possible. Since the adverse health effects of superfund chemicals are dose-dependent, the amount of the ingested material that is systemically absorbed is usually the most important parameter in determining risk. This project seeks to understand some of the factors that influence the bioavailability of superfund chemicals, including intestinal biotransformation and chronic exposure of the animal to other superfund chemicals, such as chlorinated planar polycyclic compounds, that are Ah receptor agonists. As well as inducing CYP1A1, Ah receptor agonists have numerous other biochemical and physiological effects. The investigators propose to test the hypotheses that two Ah receptor agonists found in Superfund sites, namely 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and 3,3',4,4'-tetrachlorobiphenyl (TCB) cause alterations in the physiological and structural make-up of intestinal cells that affect the intestinal bioavailability and biotransformation of lipophilic chemicals. The questions raised by these hypotheses will be investigated using in vivo, in situ and in vitro, including molecular biological, techniques with the catfish as the primary animal model. The first specific aim is to examine the intestinal biotransformation and bioavailability of radiolabeled TCB and 2,2',4,4',5,5'-hexachlorobiphenyl as well as the chlorinated solvent trichloroethene in control and TCDD- or TCB-induced catfish. The second specific aim relates to mechanisms of absorption. Although it is widely thought that lipophilic xenobiotics are absorbed solely by passive diffusion, there is evidence from previous studies that other vectorial carrier-mediated processes mediate absorption. We propose to investigate the expression of selected proteins, P-glycoprotein and glutathione S- transferases, that may be affected by Ah receptor agonists and involved in the transport of lipophilic xenobiotics in intestine of control and induced fish. These studies will provide insight into the processes affecting the dietary bioavailability of important superfund chemicals.