Repair of O6-methylguanine in adapted Escherichia coli.

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Abstract
Cells exposed to sublethal concentrations of simple alkylating agents develop resistance to their mutagenic effects. This results from the induction of a system that was called the adaptive response. During exposure to N-methyl-N''-nitro-N-nitrosoguanidine (MNNG), E. coli cells induced for the adaptive response accumulate substantially less O6-methylguanine in their DNA than control cells. If O6-methylguanine does form, adapted cells possess a repair system for removing it from their DNA. The capacity of this system is limited and the system ceases to function when too much alkylation occurred. From this point onwards O6-methylguanine starts to accumulate, and the cells begin to develop mutations at a rate directly proportional to their rate of O6-methylguanine accumulation. The O6 methylation of guanine apparently accounts for most MNNG-induced mutagenesis.