A major challenge to federal and state regulatory agencies is performing hazard and risk assessments on chemicals already in the environment, and on new chemicals whose release is proposed. The definitive experimental means for determining a material's carcinogenic potential remains the rodent lifetime bioassay. The long "in-life" phase (two years) for this study remains its major limitation and is also one of the major factors contributing to its high cost. Another limitation is the need to use large numbers of animals to detect relatively weak carcinogens. The studies represent the first phase in the validation of a transgenic mouse carcinogen bioassay which could shorten the in-life testing phase by approximately 7%. Transgenic mice expressing the pim1 oncogene (Eu-pim- 1) in lymphoid tissues are mildly predisposed toward the development of T cell lymphomas. Eu-pim-1 mice treated with the model mutagen/carcinogen ethylnitrosourea are approximately 25-fold more sensitive to the development of lymphomas than are control mice. In the studies, a model chemical, p-cresidine, currently being evaluated using other transgenic mouse models will be tested for carcinogenic activity in Eu-pim-1 mice and in non transgenic controls. p-cresidine is a genotoxic carcinogen which has been shown to induce tumors in both rats and mice. Transgenic and control mice will be treated with p-cresidine for 150 days by dosed feed. Tumor types, tumor frequencies and latency periods will be compared at the end of the study.Awardee's statement of the potential commercial applications of the research:Currently validated assays used to assess potential carcinogenicity require two years to complete and are therefore very costly. Validation of a rodent bioassay which can be performed in a four to five month period with fewer animals would effect dramatic cost savings and would have wide commercial application.National Cancer Institute (NCI)
