Molecular Analysis of Mutations in Endogenous Genes

The mutagenic potential of chemical agents and radiation is determined primarily by the nature and quantity of the lesions introduced in DNA. Most mutagens induce multiple types of lesions, each with different mutagenic properties resulting in a variety of mutations. To obtain a clear picture of the various types of mutations caused by a mutagen, target genes capable of detecting the majority of induced mutations are needed. Detecting mutations has been limited to those genes in which a mutation causes a phenotypic change such that mutants can be isolated through selective killing of cells or organisms carrying the non-mutated gene, or where the phenotypic change is recognizable by visual inspection. However, not all mutations in a gene give rise to a mutant phenotype, because some mutations either do not alter (e.g., "wobble bases") or only partially reduce the activity of the gene product.