NITRIC OXIDE IN TETRACHLORODIBENZO-P-DIOXIN (TCDD) MEDIATED TOXICITY

四氯二苯并-对-二恶英 (TCDD) 中的一氧化氮介导的毒性

• 批准号: 6340943
• 负责人: D HECK
• 金额: $ 15.68万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340943
• 关键词: dioxins; environmental toxicology; laboratory rat; nitric oxide; nitric oxide synthase; physical chemical interaction

TCCD is a ubiquitous environmental contaminant. Exposure to TCCD result in metabolic, immunologic, reproductive and neoplastic effects in animals. TCDD is a putative human carcinogen and poses a potential risk to human health. We have made the intriguing observation that TCDD up regulates expression of the cytokine inducible isoform of the enzyme nitric oxide synthase and induces nitric oxide biosynthesis by rat hepatic endothelia cells. This is the first demonstration that aryl hydrocarbons regulate an intracellular messenger in the endothelium and provides an important clue on a potential mechanism by which TCCD may alter cellular functioning and induce toxicity. It is our hypothesis that TCDD acts to induce expression of type II no synthase (N0S II) in endothelial cells and that N0 produced in response to TCDD may mediate some of the toxic effects of this contaminant. To test this hypothesis experiments are designed to analyze molecular mechanisms by which TCDD regulates N0 production, and to determine the role of N0 in TCCD-induced tissue injury in rats. These studies will provide information potentially useful for the development of clinical regimens for abrogating TCCD-induced injury in humans. These studies are important and may provide insight into one mechanism by which TCDD induces toxicity.

三氯甲烷是一种普遍存在的环境污染物。接触三氯甲烷 导致代谢、免疫、生殖和肿瘤方面的影响 动物。TCDD是一种假定的人类致癌物质，并具有潜在的 对人类健康的威胁。我们做了一个耐人寻味的观察， TCDD上调细胞因子诱导的血管内皮细胞亚型的表达 酶促一氧化氮合酶，诱导一氧化氮生物合成 大鼠肝内皮细胞。这是阿丽尔第一次演示 碳氢化合物调节内皮细胞内的信使 并提供了一条关于潜在机制的重要线索 三氯甲烷可能会改变细胞功能并引起毒性。这是我们的 TCDD诱导II型一氧化氮合酶表达的假说 (N0S II)，以及N0在响应 TCDD可能介导了这种污染物的一些毒性效应。至 检验这个假设实验是用来分析分子的 TCDD调节N0产生的机制，以及 确定N0在三氯甲烷诱导的大鼠组织损伤中的作用。这些 研究将提供可能对开发有用的信息 用于消除三氯甲烷在人体中所致损伤的临床方案。 这些研究是重要的，并可能提供对一个 TCDD的毒性机制。