Repair of O6-methylguanine in adapted Escherichia coli. 1978

P F Schendel, and P E Robins

Cells exposed to sublethal concentrations of simple alkylating agents develop resistance to their mutagenic effects. This results from the induction of a system that we have called the adaptive response. During exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), Escherichia 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 has 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. Our data support the idea that the O6 methylation of guanine accounts for most MNNG-induced mutagenesis.

UI MeSH Term Description Entries
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D008769 Methylnitronitrosoguanidine A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties. Methylnitrosonitroguanidine,Nitrosomethylnitroguanidine,Nitrosonitromethylguanidine,MNNG,N-Methyl-N'-nitro-N-nitrosoguanidine,N Methyl N' nitro N nitrosoguanidine
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D006147 Guanine
D000222 Adaptation, Physiological The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT. Adaptation, Physiologic,Adaptations, Physiologic,Adaptations, Physiological,Adaptive Plasticity,Phenotypic Plasticity,Physiological Adaptation,Physiologic Adaptation,Physiologic Adaptations,Physiological Adaptations,Plasticity, Adaptive,Plasticity, Phenotypic
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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