A SENSITIVE TRANSGENIC MODEL FOR CARCINOGEN DETECTION

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The objective of this proposal is to finish validation of a unique transgenic mouse model for applications in preclinical toxicology and risk assessment. The K6/ODC mouse overexpresses the enzyme ornithine decarboxylase in skin and internal organs and is exquisitely sensitive to topically applied carcinogens. The specific aims of the application are to determine the tumor response of K6/ODC mice to systemically administered chemicals and to continue characterization of the response to UV irradiation. Use of this model for carcinogen detection will reduce the time, cost, and number of animals required for regulatory purposes as compared to existing models. In addition, the enhanced sensitivity of the model allows agents to be tested at low doses typical of human exposure levels. PROPOSED COMMERCIAL APPLICATIONS: An in vivo transgenic mouse model will be further developed for testing the carcinogenic potential of drugs, environmental chemicals, dietary constituents, and UV light. Because the model is extremely sensitive, chemicals can be tested at low doses, comparable to human exposure levels.