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. Epidemiolog ical data suggest that BTC is a human lung carcinogen. BTC is also a c arcinogen in the A/J mouse lung tumor bioassay. Activated K-ras protoo ncogenes were detected in BTC-induced lung tumors from A/J mice. The p olymerase chain reaction was used to amplify specific DNA segments lik ely to contain activating mutations, and the amplified DNAs were seque nced 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 tr ansition in codon 12. Thus, BTC may exert its carcinogenic action by a ctivation of the K-ras protooncogene through a genotoxic mechanism.