The detection of activated protooncogenes in mouse lung
tumors has led to a major advance in our understanding of
carcinogenesis of the lung at the molecular level. A high frequency of activated K-ras protooncogenes has been detected in
tetranitromethane (TNM)- and 1,3-butadiene-induced lung
tumors in B6C3F1 mice. In the past several years, we have pursued protooncogene activation in spontaneous and chemically induced
tumors of strain A mice. The strain A mouse has a high incidence of spontaneous lung
tumors and is susceptible to
tumor induction by chemical
carcinogens. We have detected and characterized the activated protooncogenes in the
DNA of both spontaneously occurring and chemically induced lung
tumors of strain A mice. Activated K-ras genes were detected using the NIH/3T3 transfection assay, and the activating mutations were identified by utilizing the polymerase chain reaction (PCR) and direct sequence analysis. A strong selectivity of mutations in the K-ras genes were observed in chemically induced lung
tumors, as compared to spontaneous
tumors, indicating that the
carcinogens directly induced point mutations in the K-ras protooncogene. These findings suggest that the strain A mouse lung
tumor model appears to be a very sensitive system to identify the mechanism by which chemical
carcinogens activate the K-ras gene in lung tissue in vivo.