THE MUTAGENIC POTENTIAL OF SODIUM AZIDE

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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.