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 andanimal cancers. The ultimate carcinogenic form of VC, 2-chloroacetaldehyde(CAA), has been suspected to be mutagenic and we confinned themutagenicity of CAA using a modified shuttle vector plasmid.Base sequence analyses of 109 mutant plasmids with mutationsin the supF gene, which were treated with CAA and propagatedin the cultured human cells, revealed that more than half ofthe single base substitutions were G:C to A:T transitions witheight hotspots. The majority of the mutations involving G:Cbase pairs were in 5'-AAGG-3' or 5'-CCTT-3' sequences suggestingthat these sequences are the main targets of mutagenesis causedby CAA.