K-ras mutations in benzotrichloride-induced lung tumors of A/J mice.
Benzotrichloride (BTC) is used extensively as a chemical intermediate in the synthesis of benzoyl chloride and benzoyl peroxide. Epidemiological data suggest that BTC is a human lung carcinogen. BTC is also a carcinogen in the A/J mouse lung tumor bioassay. Activated K-ras protooncogenes were detected in BTC-induced lung tumors from A/J mice. The polymerase chain reaction was used to amplify specific DNA segments likely to contain activating mutations, and the amplified DNAs were sequenced to identify the mutation. The activating mutation present in the K-ras gene from all BTC-induced lung tumors (24/24) was a GC-->AT transition in codon 12. Thus, BTC may exert its carcinogenic action by activation of the K-ras protooncogene through a genotoxic mechanism.
Department of Pathology, Medical College of Ohio, Toledo 43699.
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Wang
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D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D014050:Toluene / Q000031:analogs & derivatives* / Q000633:toxicity
D014050:Toluene; C018847:benzotrichloride