BIOVAILABILITY OF SUPERFUND CHEMICALS

超级基金优先有机化学品可能进入人类食物链， 很多路。 在这些化学物质渗入水体的地区， 这些化学物质可能会被当地的鱼类和贝类吸收， 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。 因为对健康的不良影响 的超级基金化学品是剂量依赖性的，摄入的量 被全身吸收的物质通常是最重要的 确定风险的参数。 本项目旨在了解一些 影响超级基金化学品生物利用度的因素， 包括动物的肠道生物转化和长期接触 其他超级基金化学品，如氯化平面多环 作为Ah受体激动剂的化合物。 除了诱导CYP 1A 1， Ah受体激动剂具有许多其他生物化学和生理学特性， 方面的影响. 研究人员提出要检验两个Ah 受体激动剂，即2，3，7，8- 四氯二苯并对二恶英（TCDD）和3，3 '，4，4'-四氯联苯 (TCB)导致生理和结构组成的改变 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。 这些问题引起的 假设将使用体内，原位和体外， 包括分子生物学技术， 主要动物模型。 第一个具体目标是审查 放射性标记TCB的肠道生物转化和生物利用度， 2，2 '，4，4'，5，5 '-六氯联苯以及氯化溶剂 三氯乙烯对照组和TCDD或TCB诱导的鲶鱼。 第二 具体目标涉及吸收机制。 虽然人们普遍 认为亲脂性外源性物质仅被被动吸收， 扩散，有证据表明，从以前的研究，其他矢量 载体介导的过程介导吸收。 我们建议调查 选择的蛋白质、P-糖蛋白和谷胱甘肽S- 转移酶，其可能受Ah受体激动剂影响并涉及 在对照组肠道中亲脂性外源性物质的转运中， 诱鱼 这些研究将提供深入了解的过程， 影响重要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.