Studies on oncogene activation in spontaneous and chemically induced rodent neoplasms started several years ago in collaboration with molecular biologists at NIEHS and are continuing. Samples are obtained from both the National Toxicology Program bioassays and from rodent studies designed to investigate the pathogenesis of neoplasia and strain susceptibility to genotoxic and nongenotoxic agents. Current work has been expanded to investigate the role of suppressor genes and growth factors in carcinogenesis to identify susceptibility factors that impact on carcinogenesis. Recent work has shown that oncogene activation in lung and liver tumors is influenced by the dose of carcinogen. It has also been shown that chlordane-induced liver tumors in B6C3F1 mice lack any evidence of oncogene activation and that these tumors regress when treatment is withdrawn. Work on mice carrying single and dual transgenes is underway to determine the role these genes play in the pathogenesis of hepatocarcinogenesis. Studies on the expression of TGF-a, IGF-II, cyclin D1 and myc in spontaneous mouse hepatocellular carcinomas have recently been completed.
