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

Carcinogenesis. 1993 May;14(5):789-94. doi: 10.1093/carcin/14.5.789.

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 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Composition
  • Base Sequence
  • Carcinogens / pharmacology*
  • DNA, Bacterial / genetics
  • Environmental Pollutants / toxicity
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Frameshift Mutation
  • Genes, Bacterial / drug effects*
  • Methylene Chloride / pharmacology*
  • Molecular Sequence Data
  • Mutagens / pharmacology*
  • Point Mutation*
  • Ultraviolet Rays

Substances

  • Carcinogens
  • DNA, Bacterial
  • Environmental Pollutants
  • Mutagens
  • Methylene Chloride