METABOLIC ACTIVATION OF ARYLAMINES IN LEUKOCYTES

白细胞中芳胺的代谢激活

• 批准号: 3251128
• 负责人: MICHAEL D CORBETT
• 金额: $ 6.75万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-06-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3251128
• 关键词: DNA; N acylation; RNA; acylation; aniline; biphenylamines; bone marrow; cell type; centrifugation; chemical binding; chemical reaction; chemical structure function; chemical synthesis; covalent bond; cyclic amine; high performance liquid chromatography; human tissue; hydroxamate; leukocytes; macrophage; monocyte; neutrophil; nitrosamines; phenylamide; scintillation counter; sedimentation; tissue /cell culture; toxicant interaction; toxin metabolism

The purpose of this program is to elucidate certain biochemical processes that are partially responsible for the genotoxicity of arylamines and nitroso aromatic compounds. The arylamines constitute some of our most important chemicals. Arylamines and derivatives are common pharmaceutical agents and the extensive use of arylamine derivatives as pesticides in modern agricultural practice continues to increase. On the other hand, a knowledge of the biological fate and effects of arylamines in living organisms is very incomplete. Since many arylamines and related chemicals are known carcinogens, it is necessary that a detailed knowledge of the metabolism of these chemicals in higher animals be attained. This program will study the extent to which model aromatic amines are metabolized to hydroxamic acids, since hydroxamic acids are known to account for much of the toxicity of aromatic amines. The program will examine the biochemical processes that convert nitroso aromatic compounds to hydroxamic acids possessing unusual N-acyl groups. The specific biochemical pathways responsible for such hydroxamic acids arise from the interaction of a nitroso aromatic compound with a thiamin-dependent enzyme. Another facile, but non-enzymatic reaction that causes the production of the N-formyl type hydroxamic acid under physiological conditions is the reaction a nitroso aromatic with glyoxylic acid. The bioactivation reactions of interest will be studied by employing leukocytes, since these blood cells comprise sizable and highly disseminated tissues. Total and purified leukocyte types (neutrophils, monocytes, macrophages, lymphocytes) will be obtained from New Zealand white rabbits, Syrian golden hamsters, Sprague Dawley rats and banked human blood. The results of this program will provide valuable data to help design measures to minimize mankind's exposure to, or damage from, potentially genotoxic chemicals.

本节目的目的是阐明某些生化过程。 对芳胺类化合物的遗传毒性负有部分责任 亚硝基芳香族化合物。芳胺构成了我们最重要的 重要的化学品。芳香胺及其衍生物是常见的药物。 药剂和芳胺衍生物作为杀虫剂在 现代农业实践活动持续增多。另一方面，一个 对芳香胺的生物命运和对生命的影响的认识 生物体是非常不完整的。由于许多芳胺和相关化学品 都是已知的致癌物，有必要详细了解 这些化学物质在高等动物体内的新陈代谢是可以实现的。本节目 将研究模型芳香胺代谢到何种程度 异羟肟酸，因为已知异羟肟酸占很大一部分 芳香胺的毒性。该程序将检查生化 将亚硝基芳香族化合物转化为异羟肟酸的过程 具有不寻常的N-酰基的。特定的生化途径 负责这种异羟肟酸的产生是由一种 亚硝基芳香化合物与硫胺素依赖的酶。另一个轻而易举的， 但非酶反应导致N-甲酰型的产生 异羟肟酸在生理条件下是亚硝基的反应 芳香的乙醛酸味。感兴趣的生物活化反应将 通过使用白细胞进行研究，因为这些血细胞包括 大小和高度分散的组织。总白细胞和纯化白细胞 将获得各种类型(中性粒细胞、单核细胞、巨噬细胞、淋巴细胞) 来自新西兰白兔、叙利亚金黄仓鼠、SpragueDawley大鼠 还储存了人类的血液。这项计划的结果将提供有价值的 数据，以帮助设计措施，最大限度地减少人类的暴露或损害 来自可能具有遗传毒性的化学物质。