Our major focus continues to be the analysis of protooncogene activation in rodent and human tumors, and mouse lung tumor susceptibility at the K-ras locus. Previously, activated protooncogenes were detected in 12 of 14 human lung tumors. Portions of two non-ras genes were cloned. The first non-ras gene has been localized to chromosome 10p by in situ hybridization and the cloned sequences were used to obtain a cDNA clone that gave tumors in the nude mouse tumorigenicity assay with a short latency. A single human DNA fragment of 16kbp had been cloned from the second non-ras gene human lung tumors and used to localize this gene to chromosome 20 by in situ hybridization. An additional set of human pulmonary squamous cell carcinomas have been analyzed for activated protooncogenes using the nude mouse tumorigenicity assay. Transfections indicated that 5 of 16 of these carcinomas contained detectable transforming genes that were not H-, K-, or, N-ras or c-raf genes and some of these tumors may contain the same alu bands as determined by Southern blot analysis. Rat lung tumors from animals treated with diethylnitroamine (DEN) and promoted with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) scored positive in the tumorigenicity assay for oncogenes. The analysis of highly conserved DNA fragments suggested that the same gene was activated in each of the adenocarcinomas. To explore the genetics of the K-ras gene in mouse lung tumor susceptibility, the parental origin of K-ras genes detected in lung tumors from F1 hybrids was determined. K-ras oncogenes were derived from the susceptible A/J patent in 38/40 tumors from C3A hybrid mice and 30/30 tumors from AC3 hybrid mice. This observation suggests that the K-ras gene is directly linked to mouse lung tumor susceptibility.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
United States
Zip Code