PRODUCTION AND FATE OF HYDROXAMIC ACIDS IN HEPATOCYTES

这个程序的目的是阐明某些生化过程 与芳香胺和亚硝基芳香胺的毒性有关， 化合物. 作为一个群体，芳香胺包含了人类最重要的 重要的工业化学品。 它们广泛用作杀虫剂， 现代农业实践继续增加，但知识， 它们在生物体中的生物命运和影响非常不完整。 由于许多芳香胺和相关化学物质是已知的致癌物质， 有必要详细了解这些化学物质的代谢 在高等动物中可以达到。 该计划将研究在多大程度上， 模型芳族胺代谢为异羟肟酸，因为异羟肟酸 已知酸是芳香胺毒性的主要原因。 该计划将研究的生化过程，转化亚硝基 芳香族化合物到具有不寻常的N-酰基的异羟肟酸。 负责这种异羟肟酸的特定生化途径 由亚硝基芳族化合物与 硫胺素依赖酶 另一个简单的，但非酶反应， 导致N-甲酰基型异羟肟酸产生的反应是 亚硝基芳香剂和乙醛酸的混合物。 原代肝细胞培养物 将是这些研究的主要系统， 进行，尽管出于比较目的，原代肝细胞培养 也将使用叙利亚仓鼠。 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 暴露于潜在的遗传毒性化学品或受到其损害。

The purpose of this program is to elucidate certain biochemical processes that are involved in the toxicity of aromatic amines and nitroso aromatic compounds. As a group the aromatic amines comprise some of mankind's most important industrial chemicals. Their extensive use as pesticides in modern agricultural practice continues to increase, yet a knowledge of their biological fate and effects in living organisms is very incomplete. Since many aromatic amines 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 thiamine-dependent enzyme. Another facile, but non-enzymatic reaction that causes the production of the N-formyl type hydroxamic acids is the reaction of a nitroso aromatic with glyoxylic acid. Primary hepatocyte cultures prepared from rats will be the principal system in which these studies will be conducted, although for comparative purposes primary hepatocyte cultures for syrian hamsters will also be used. 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.