MUTATIONAL SPECIFICITIES OF ENVIRONMENTAL CARCINOGENS IN THE LACI GENE OF ESCHERICHIA-COLI .6. ANALYSIS OF METHYLENE CHLORIDE-INDUCED MUTATIONAL DISTRIBUTION IN UVR- STRAINS( AND UVRB)

To better understand the mechanisms of mutagenesis by the carcinogen, methylene chloride (DCM), we have determined the nature and distributi on of forward mutations induced by DCM in the N-terminal region of the lacI 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 str ains base substitutions predominated (74-88%) the distribution among t he classes differed. In the case of the Uvr+ strain, DCM substantially increased the frequency of G:C --> C:G transversion and duplication e vents. Direct repeats were not observed at the endpoints of the duplic ations, 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-i nduced mutation.