Induction of specific base-pair substitutions in E. coli trpA mutants by chloroethylene oxide, a carcinogenic vinyl chloride metabolite.

Chloroethylene oxide (CEO), an ultimate carcinogenic metabolite of vinyl chloride, induces base-pair substitution mutations but not frameshift mutations in bacteria. The mutational specificity of CEO was investigated in Escherichia coli, using the trpA mutants developed by Yanofsky. Reversion frequencies to tryptophan prototrophy were analysed, and CEO was found to induce more GC----AT transitions than AT----TA transversions, in addition to a low frequency of other types of substitution. This specificity indicates that CEO is mutagenic through a miscoding DNA adduct. The results are discussed in relation to the various CEO-DNA adducts formed and to their reported or expected mispairing properties.