Chloroacetaldehyde-induced mutagenesis in Escherichia coli: specificity of mutations and modulation by induction of the adaptive response to alkylating agents.
The mutational specificity of chloroacetaldehyde (CAA), one of the metabolites of the human carcinogen vinyl chloride (VC), has been determined through the examination of Arg+ revertants in Escherichia coli AB2497 (Arg-) and identification of their tRNA suppressors. The predominant mutations were GC-->AT transitions (65%) followed by AT-->TA transversions (12.5%). The observed mutational specificity of CAA is very similar to the reported specificity of the other VC metabolite, chloroethylene oxide. The induction of the adaptive response to alkylating agents significantly decreased the frequency of CAA-induced Rifr and Arg+ mutants in E. coli AB2497 and increased the cell survival. Likewise, the adaptation of bacterial cells decreased the frequency of GC-->AT transitions in CAA-treated M13glyU phage transformed to E. coli JC15419 and increased the phage survival. Experiments with strain MS23, which is an alkA mutant deficient in 3-methyladenine-DNA glycosylase II, and with MS23 harboring the pYN1000 plasmid carrying the alkA+ gene, have shown that induction of this repair enzyme is responsible for reduction of the level of CAA-induced mutations. The role of N2,3-ethenoguanine, among the other etheno-adducts, in CAA-induced mutagenesis and as a target for repair in 3-methyladenine-DNA glycosylase II proficient bacterial cells is discussed.
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa.
M M
MM
Mroczkowska
I K
IK
Kolasa
J T
JT
Kusmierek
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D000477:Alkylating Agents / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D004269:DNA, Bacterial / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D005798:Genes, Bacterial; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D016296:Mutagenesis; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D014752:Vinyl Chloride / Q000378:metabolism / Q000633:toxicity
D000477:Alkylating Agents; D002273:Carcinogens; D004269:DNA, Bacterial; D008769:Methylnitronitrosoguanidine; D008741:Methyl Methanesulfonate; C004656:chloroacetaldehyde; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D000079:Acetaldehyde; D014752:Vinyl Chloride