Isolation of Mutants of Escherichia coli with Increased Resistance to Alkylating Agents
A search was made for strains constitutive for the adaptive response by isolating mutants with increased resistance to killing by methylating agents. N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) resistant strains were obtained, but these proved to be less readily methylated by MNNG because they had a low intracellular thiol content (thiols convert MNNG to the proximal mutagen, methylnitrosamine (5)). Four strains with increased resistance to N-methylnitrosourea (MNU) proved to be constitutive for the adaptive response. After exposure to (3H) MNNG, they showed the same low ratio of O6-methylguanine (O6MeG) to 7-methylguanine (N7MeG) as adapted wild type bacteria. When exposed to very high MNNG doses, they were even more resistant to killing and mutation than the adapted wild type. The constitutives may therefore have an even greater ability than the adapted wild type to repair O6MeG.
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