Physiological modification of alkylating-agent induced mutagenesis. I. Effect of growth rate and repair capacity on nitrosomethylurea-induced mutation of Escharichia coli.

The effects of repair capacity and growth rate on the induction of mutations by N-methyl-N-nitosourea (MNUA) was investigated using the trpE reversion system of Escherichia coli WP2 and some repair-deficient derivatives isogenic for this gene. In all these strains reducing the growth rate prior to MNUA-treatment caused a reduction in the mutational response, however major differences were observed between strains. In exrA and recA- bacteria stationary phase cells were 100 times less mutable than cells grown at a mean generation time (m.g.t.) of 30 min, whereas reductions of 12 and 25 times were observed in the uvrA- and wild-type strains respectively. In contrast the mutational response of the polA- mutant varied only slightly with growth rate; the increases at high MNUA concentrations being equal to the increase in the trpE gene number. These results show the increasing importance of the error-prone exrA+/recA+-dependent repair system in mutation-induction by MNUA as the growth rate of the culture is reduced and its relative unimportance for mutation induction in nutrient broth-grown cells (m.g.t. 30 min).