title: Isolation and characterization of Escherichia coli K-12 mutants unable to induce the adaptive response to simple alkylating agents.
abstract: When Esherichia coli cells are exposed to a low level of simple alkylating agents, they induce the adaptive response which renders them more resistant to the killing and the mutagenic effects of the same or other alkylating agents. This paper describes the isolation of one strain that was deficient in mutagenic adaptation and five that were deficient in both mutagenic and killing adaptation, confirming previous suggestions that killing and mutagenic adaptation are, at least to some extent, separable. These six strains have been called Ada mutants. They were more sensitive to the killing and mutagenic effects of N-methy-N'-nitro-N-nitrosoguanidine (MNNG) than the unadapted Ada+ parent. Thus, the adaptation pathway is responsible for circumventing some alkylation-induced damage even in cells that are preinduced. The increase in mutation frequency seen in Ada cells treated with MNNG was the same whether the cells were lexA+ or lexA, showing that the extra mutations found in Ada- strains do not depend upon the SOS pathway. Ada strains accumulated more O6-methyl guanine lesions than the Ada+ parent on prolonged exposure to MNNG, and this supports the idea that O6-methyl guanine is the most important lesion for MNNG-induced mutagenesis. The ada mutations have been shown to map in the 47 to 53-min region of the E. coli chromosome.
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D003433:Crosses, Genetic; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D009154:Mutation / Q000187:drug effects*
chemical_list: D000477:Alkylating Agents