Adaptive response to simple alkylating agents in Bacillus subtilis cells

Abstract When the cells of Bacillus subtilis Marburg strains were grown in the presence of N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG) at a non-toxic concentration, they acquired resistance with regard to both lethality (enhancement of survival) and mutagenicity (reduction of mutation frequency) to subsequent challenge with MNNG at higher concentrations. Thus, like Escherichia coli cells (Samson and Cairns, 1977), B. subtilis cells respond adaptively to MNNG. Protein synthesis was necessary for the adaptation, and an activity to destroy specifically O 6 -methylguanine residues in methylated DNA was present in the extracts of the adapted cells. Therefore, this response is attributable to an error-free DNA-repair system induced by the exposure to MNNG. The adaptive response was observed with the cells carrying uvrA, polA or recA mutation, indicating this to be independent of the excision repair or recA -dependent repair. For the acquisition of the resistance to MNNG, methylating or ethylating agents were effective, but neither N -butyl- N -nitrosorea (BNU) nor N -propyl- N ′-nitro- N -nitrosoguanidine (PNNG) was effective. The cells pre-treated with MNNG became resistant to the challenge with alkynitrosoureas or N -alkyl- N ′-nitro- N -nitrosoguanidine, but not to the challenge with methyl methanesulphonate (MMS) or dimethyl sulphate (DMS). Thus, the target of the induced DNA-repair activity is likely to be O -alkylated bases in DNA. Though the phenomenology of the adaptive response seems similar to that in E. coli , the following two lines of evidence indicate that the underlying mechanisms may not be identical: (1) in B. subtilis , the cells of polA strains are adapted both with regard to lethality and to mutagenicity; (2) in B. subtilis , MMS or DMS acts only as the inducer of the response.