To determine if transgenic mouse strains carrying activated oncogenes are more sensitive to the to the carcinogenic effects of certain chemicals than noncarrier littermates. Specifically to determine if carcinogenic effects can be detected with shorter duration studies than current 24 month carcinogenicity studies, and if transgenic mice exhibit a pattern of chemically induced tumors distinct from the spontaneous pattern characteristic for the activated oncogene which they inherit. The results from these studies may also provide an indication of the utility of these transgenic mouse strains for mechanistic studies of chemical carcinogenesis. Two chemicals (p-cresidine, a mutagenic multisite carcinogen and reserpine, a non-mutagenic mammary carcinogen) previously tested by NCI/NTP will be utilized for this project. A 14-day repeated dose study will be conducted to determine if significant differences exist between the toxicity of the test chemicals in three transgenic mouse strains, their noncarrier littermates and B6C3F1 mice and to set doses for the 6-9 month carcinogenicity study. The carcinogenicity study will determine and characterize the carcinogenic effects of these chemicals in transgenic mice.
