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被用作除草剂、杀菌剂和 杀线虫剂。 此外，该化合物已被测试为 氮气用于汽车安全气囊充气和释放机构 飞机逃生滑道。 这种简单的化合物在 多种原核生物和植物物种。 事实上，它是最 已知有效的植物诱变剂。 多次尝试引发诱变 哺乳动物细胞的反应表明这种化合物最多 弱致突变性。 对于这种差异的一种可能的解释 致突变性在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，已证明这种致突变代谢物 是叠氮丙氨酸，由叠氮化物在体内产生 半胱氨酸生物合成途径中的取代。 因此，该化合物 具有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，因此评估叠氮化物非常重要 人类接触致突变中间体的潜在风险。 确实，一个 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，这种化学物质还具有 诱变剂具有独特的特性，无论是在其激活机制还是 在其作用方式中。 因此，叠氮化物是用于以下领域的理想化合物： 揭示诱变的分子机制。 试图了解这些过程并评估诱变性 叠氮化物诱变中间体对哺乳动物细胞的影响 提议研究叠氮丙氨酸和叠氮乙胺对 各种遗传参数。 这将包括评估以下措施的影响： 这些代谢物影响人类成纤维细胞的姐妹染色单体交换 和中国仓鼠细胞，以及增加与基因的相关性 Na/K ATPase 和 HGPRT 位点均发生突变。 此外，它是 提议确定哺乳动物细胞将叠氮化物转化为 假定的诱变中间体。