THE MUTAGENIC POTENTIAL OF SODIUM AZIDE

叠氮钠多年来一直被用作除草剂、杀菌剂和 杀线虫。此外，这种化合物已经被测试为一种 汽车安全气囊充气用氮气及其释放机构 飞机逃生降落伞。这种简单的化合物在一种 原核生物和植物种类的多样性。事实上，它是世界上最大的 已知的高效植物诱变剂。几次尝试诱变诱变剂 哺乳动物细胞的反应表明，这种化合物充其量是 弱致突变性。对这种差异的一种可能的解释 致突变性在于将叠氮转化为 对观察到的叠氮化合物负有最终责任的中间体 诱变。最近，IS被证明这种诱变代谢物 是叠氮丙氨酸，它是由叠氮在体内产生的 半胱氨酸生物合成途径中的取代。因此，这种化合物 提供了成为主要环境诱变剂的潜力。 由于叠氮是一种常用的化学物质，因此评估 人类接触致突变中间体的潜在风险。事实上，一个 对这种化合物的诱变潜力有深入的了解 哺乳动物细胞将导致对适当安全性的更好评估 人类人口的水平。此外，这种化学物质还具有 在诱变剂中独一无二的性质，无论是在其激活机制上还是在 在其行动模式中。因此，叠氮化合物是用于 揭开诱变的分子机制(S)。 试图了解这些过程并评估诱变剂 叠氮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姐妹染色单体交换的影响 和中国仓鼠细胞，以及增加与基因的相关性 Na/K-ATPase和HGPRT基因座的突变。此外，它是 建议确定哺乳动物细胞将叠氮转化为 一种可能的诱变中间体。

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.