Mutational specificities of environmental carcinogens in the lacI gene of Escherichia coli. VI: analysis of methylene chloride-induced mutational distribution in Uvr+ and UvrB− strains

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Abstract
To better understand the mechanisms of mutagenesis by the carcinogen, methylene chloride (DCM), we have determined the nature and distribution of forward mutations induced by DCM in the N-terminal region of the lacl gene of Escherichia coli. A total of 116 lacI−d mutations (50 from Uvr+, 66 from UvrB− strain) were characterized by DNA sequencing. Both similarities and differences were observed. Although in both strains base substitutions predominated (74–88%) the distribution among the classes differed. In the case of the Uvr+ strain, DCM substantially increased the frequency of G:C ↑ C:G transversion and duplication events. Direct repeats were not observed at the endpoints of the duplications, however, all endpoints were in an A: T-rich region. In contrast, in the UvrB− strain, DCM induced A:T ↑ G:C, A:T ↑ C:G, G:C ↑ C:G events as well as deletions. The mutational spectra presented here represent a first step in the elucidation of the mechanism(s) of DCM-induced mutation.

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