ARYL HYDROCARBON SIGNAL TRANSDUCTION MECHANISMS IN FISH

鱼类中芳基烃信号转导机制

• 批准号: 2414963
• 负责人: WADE H POWELL
• 金额: $ 2.43万
• 依托单位: WOODS HOLE OCEANOGRAPHIC INSTITUTION
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-31 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2414963
• 关键词: aromatic hydrocarbon receptor; biological signal transduction; cycloalkene; molecular cloning; protein structure function; trout /salmon

The overall objective of this project is to understand the molecular mechanisms of the toxic effects of dioxin and other halogenated aromatic hydrocarbons (HAH) in fish, using the estuarine teleost Fundulus heteroclitus as a model system. These compounds are common pollutants which result from many manufacturing processes. Their effects, including tumor promotion, teratogenesis, immunosuppression, and wasting, are mediated through an intracellular receptor. Although the basic scheme of HAH signal transduction is thought to be conserved between vertebrate species, the wide interspecific range of HAH toxicity, the large variation in molecular mass of HAH receptors (AhR) in different species, and the recent discovery of multiple forms of AhR in F. heteroclitus suggest that key differences may exist Specific aims of this project are (1) to clone the aryl hydrocarbon receptor nuclear translocator (ARNT) gene or genes in this species, (2) to characterize interactions between ARNT(s), the multiple AhR forms, and their target DNA sequences, and (3) to identify tissue specific patterns of expression of AhR and ARNT genes which may govern their physiological roles. The study of HAH signal transduction in fish is important for the validation of fish as model systems for in vivo toxicological testing of compounds posing potential human hazards. Knowledge of the molecular mechanisms governing the metabolism and accumulation of HAH compounds in fish will also have important implications for the assessment of the safety of fish consumption by humans and the use of fish as biomarkers for pollutant exposure.

这个项目的总体目标是理解分子 二恶英等卤代芳香族化合物的毒性作用机理 利用河口硬骨鱼束对鱼类中的碳氢化合物(HAH)进行研究 异纹藻作为一个模型系统。这些化合物是常见的污染物。 这是由许多制造工艺造成的。它们的影响，包括 肿瘤的促进、致畸、免疫抑制和消瘦是 通过细胞内的受体进行调节。虽然基本方案是 HAH信号转导被认为在脊椎动物之间是保守的 种间HAH毒性范围广，毒性大 不同物种HAH受体(AhR)分子质量的差异， 以及最近在异地锦鸡儿中发现的多种形式的AhR 暗示可能存在的主要差异本项目的具体目标是 (1)克隆芳烃受体核转位蛋白(ARNT) 该物种中的一个或多个基因，(2)描述 Arnt(S)、多种AhR形式及其靶序列，以及(3) 鉴定AhR和Arnt基因的组织特异性表达模式 这可能决定了它们的生理作用。HAH信号的研究 FISH中的转导对于FISH作为模型的有效性很重要 潜在化合物的体内毒理学测试系统 对人类的危害。对控制细胞生长的分子机制的了解 HAH化合物在鱼体内的代谢和积累也会对 对鱼类安全性评估的重要影响 人类的消费和使用鱼类作为污染物的生物标志物 曝光。