THE MUTAGENIC POTENTIAL OF SODIUM AZIDE

叠氮化钠的致突变潜力

• 批准号: 3438118
• 负责人: Pablo Arenaz
• 金额: $ 6.07万
• 依托单位: UNIVERSITY OF TEXAS EL PASO
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-16 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438118
• 关键词: adenosinetriphosphatase; azides; biotransformation; chemical structure function; environmental contamination; fibroblasts; gene mutation; high performance liquid chromatography; human tissue; hypoxanthine phosphoribosyltransferase; mutagen testing; mutagens; physical chemical interaction; tissue /cell culture

Sodium azide has been used for years as an herbicide, fungicide and nematocide. In addition, this compound has been tested as a source of nitrogen gas for automobile air bag inflation and in release mechanisms for airplane escape chutes. This simple compound is highly mutagenic in a variety of prokaryotic and plant species. In fact, it is one of the most efficient plant mutagens known. Several attempts to elicit a mutagenic response in mammalian cells have suggested that this compound is at best weakly mutagenic. One possible explanation for this differential mutagenicity lies in the mechanism used to convert azide into an intermediate that is ultimately responsible for the observed azide mutagenesis. Recently, is was demonstrated that this mutagenic metabolite is azidoalanine, which is produced in vivo as a result of an azide substitution in the cysteine biosynthetic pathway. Thus, this compound offers the potential of becoming a major environmental mutagen. As azide is a commonly used chemical, it is important to assess the potential risk of human exposure to the mutagenic intermediate. Indeed, a thorough understanding of the mutagenic potential of this compound in mammalian cells will lead to a better evaluation of the proper safety levels for human populations. In addition, this chemical possesses properties unique among mutagens, both in its mechanism of activation and in its mode of action. As a result, azide is the ideal compound to use in unraveling the molecular mechanism(s) of mutagenesis. In an attempt to understand these processes and to evaluate the mutagenic effects of the azide mutagenic intermediate on mammalian cells, it is proposed to study the effects of azidoalanine and azidoethylamine on various genetic parameters. This will include evaluating the effects of these metabolites on sister chromatid exchange in both human fibroblasts and Chinese hamster cells, and the correlation of the increase with gene mutation at both the Na/K ATPase and HGPRT loci. In addition, it is proposed to determine the ability of mammalian cells to convert azide into a putative mutagenic intermediate.

叠氮化钠多年来一直用作除草剂、杀真菌剂和杀菌剂。 杀线虫剂 此外，该化合物已被测试为 用于汽车安全气囊充气的氮气和用于 飞机逃生滑道。 这种简单的化合物在一种 各种原核生物和植物物种。 事实上，它是世界上 已知的高效植物诱变剂。 几次尝试引发突变 在哺乳动物细胞中的反应表明，这种化合物充其量是 弱致突变性 这种差异的一种可能解释是 致突变性在于用于将叠氮化物转化为 最终导致观察到的叠氮化物的中间体 诱变 最近，研究表明，这种诱变代谢物 是叠氮丙氨酸，其作为叠氮化物的结果在体内产生， 半胱氨酸生物合成途径中的取代。 因此，该化合物 提供了成为主要环境诱变剂的潜力。 由于叠氮化物是一种常用的化学品， 人类暴露于致突变中间体的潜在风险。 确实 彻底了解该化合物的致突变潜力， 哺乳动物细胞将导致更好地评估适当的安全性 人类的水平。 此外，该化学品还具有 在诱变剂中，无论是在其激活机制， 在它的行动模式。 因此，叠氮化合物是用于 揭示诱变的分子机制。 为了理解这些过程并评估致突变性， 叠氮化物致突变中间体对哺乳动物细胞的影响， 建议研究叠氮丙氨酸和叠氮乙胺对 各种遗传参数。 这将包括评估 这些代谢物对两种人成纤维细胞中姐妹染色单体交换的影响 和中国仓鼠细胞，以及与基因的相关性增加 Na/K ATP酶和HGPRT基因座突变。 此外还 建议确定哺乳动物细胞将叠氮化物转化为 一种假定的诱变中间体