A SENSITIVE TRANSGENIC MODEL FOR CARCINOGEN DETECTION

本提案的目的是完成一种独特的转基因小鼠模型的验证，用于临床前毒理学和风险评估。K6/ODC小鼠在皮肤和内脏器官中过表达鸟氨酸脱羧酶，对局部应用的致癌物非常敏感。该应用程序的具体目的是确定K6/ODC小鼠对系统给药化学物质的肿瘤反应，并继续表征对紫外线照射的反应。与现有模型相比，将该模型用于致癌物检测将减少时间、成本和监管目的所需的动物数量。此外，该模型的灵敏度提高，使药剂可以在人类典型接触水平的低剂量下进行测试。拟议的商业应用：将进一步开发体内转基因小鼠模型，用于测试药物、环境化学物质、饮食成分和紫外线的致癌潜力。由于该模型非常敏感，化学物质可以在与人类接触水平相当的低剂量下进行测试。

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.