ARYL HYDROCARBON SIGNAL TRANSDUCTION MECHANISMS IN FISH

鱼类中芳基烃信号转导机制

基本信息

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
项目类别：
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

项目摘要

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.

该项目的总体目的是了解分子二恶英和其他卤化芳族的毒性作用的机制鱼中的碳氢化合物（HAH），使用河口遗嘱作为模型系统的杂体。这些化合物是常见的污染物这是由许多制造过程产生的。它们的效果，包括肿瘤促进，致病发生，免疫抑制和浪费是通过细胞内受体介导。虽然是基本方案 HAH信号转导被认为是脊椎动物之间的保守物种，种间种间的HA毒性范围，大型不同物种中HAH受体（AHR）分子质量的变化，以及最近在F. heteroclitus中发现了多种形式的AHR 表明该项目的特定目的可能存在主要差异（1）克隆芳基碳氢化合物受体核转运剂（ARNT）该物种中的基因或基因，（2）表征 ARNT（S），多个AHR形式及其靶DNA序列，（3）鉴定组织特异性AHR和ARNT基因表达模式这可能控制其生理角色。 HAH信号的研究鱼的转导对于验证鱼作为模型很重要体内体内毒理学测试的系统人类危害。了解有关分子机制的知识鱼类中HAH化合物的代谢和积累也将有评估鱼安全的重要意义人类的消费和将鱼作为污染物的生物标志物接触。