Molecular analysis of mutations induced by 2-chloroacetaldehyde, the ultimate carcinogenic form of vinyl chloride, in human cells using shuttle vectors.
Vinyl chloride (VC) is a carcinogen associated with human and animal cancers. The ultimate carcinogenic form of VC, 2-chloroacetaldehyde (CAA), has been suspected to be mutagenic and we confirmed the mutagenicity of CAA using a modified shuttle vector plasmid. Base sequence analyses of 109 mutant plasmids with mutations in the supF gene, which were treated with CAA and propagated in the cultured human cells, revealed that more than half of the single base substitutions were G:C to A:T transitions with eight hotspots. The majority of the mutations involving G:C base pairs were in 5'-AAGG-3' or 5'-CCTT-3' sequences suggesting that these sequences are the main targets of mutagenesis caused by CAA.
Matsuda
T
T
Center for Environmental Quality Control, Kyoto University, Shiga, Japan.
Yagi
T
T
Kawanishi
M
M
Matsui
S
S
Takebe
H
H
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000633:toxicity; D001482:Base Composition; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002461:Cell Line, Transformed; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005798:Genes, Bacterial / Q000187:drug effects*; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010957:Plasmids; D017354:Point Mutation; D013539:Simian virus 40 / Q000235:genetics; D014752:Vinyl Chloride / Q000633:toxicity
D002273:Carcinogens; D017931:DNA Primers; C004656:chloroacetaldehyde; D000079:Acetaldehyde; D014752:Vinyl Chloride