METABOLIC ACTIVATION OF ARYLAMINES IN LEUKOCYTES

白细胞中芳胺的代谢激活

• 批准号: 3251127
• 负责人: MICHAEL D CORBETT
• 金额: $ 6.04万
• 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 1988-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3251127
• 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.

这个程序的目的是阐明某些生化过程 部分负责芳胺的遗传毒性， 亚硝基芳香族化合物。 芳胺构成了我们最重要的 重要化学品 芳胺及其衍生物是常用的药物 以及芳胺衍生物作为杀虫剂在 现代农业不断发展。 另一方面 了解芳胺在生活中的生物命运和影响 有机体是非常不完整的。 由于许多芳胺和相关化学品 是已知的致癌物质，有必要详细了解 这些化学物质在高等动物体内的代谢。 这个程序 将研究模型芳香胺代谢的程度， 异羟肟酸，因为已知异羟肟酸占大多数 芳香胺的毒性。 这个程序将检测 将亚硝基芳族化合物转化为异羟肟酸的方法 具有不寻常的N-酰基。 特定的生化途径 负责这类异羟肟酸的是由以下物质的相互作用引起的： 亚硝基芳香族化合物与硫胺素依赖性酶。 另一个肤浅的， 但非酶促反应导致N-甲酰基型 异羟肟酸在生理条件下的反应是亚硝基 乙醛酸芳香。 感兴趣的生物活化反应将 可以通过使用白细胞来研究，因为这些血细胞包括 巨大且高度扩散的组织。 总白细胞和纯化白细胞 将获得类型（中性粒细胞、单核细胞、巨噬细胞、淋巴细胞） 来自新西兰白色兔、叙利亚金仓鼠、Sprague道利大鼠 和储存的人血 该计划的结果将提供有价值的 数据，以帮助设计措施，以尽量减少人类的接触，或损害 潜在的基因毒性化学物质。