Proliferation of mutators in a cell population

A Lac(-) strain of Escherichia coli that reverts by the addition of a G to a G-G-G-G-G-G sequence was used to study the proliferation of mutators in a bacterial culture, Selection for the Laci phenotype, which is greatly stimulated in mismatch repair-deficient strains, results in an increase in the percentage of mutators in the selected population from less than 1 per 100,000 cells to 1 per 200 cells, All the mutators detected were deficient in the mismatch repair system, Mutagenesis results in a Similar increase in the percentage of mutators. Mutagenesis combined with a single Selection can result in a population of more than 50% mutators when a sample of several thousand cells is grown out and selected. Mutagenesis combined with two or more successive selections can generate a population that is 100% mutator, These experiments are discussed in relation to ideas that an early step in carcinogenesis is the creation of a mutator phenotype.