A SENSITIVE TRANSGENIC MODEL FOR CARCINOGEN DETECTION

这项建议的目标是完成对一种独特的转基因小鼠模型的验证，以应用于临床前毒理学和风险评估。K6/ODC小鼠在皮肤和内脏过度表达鸟氨酸脱羧酶，对局部应用的致癌物非常敏感。该应用的具体目的是确定K6/ODC小鼠对全身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，使用该模型进行致癌物检测将减少监管所需的时间、成本和动物数量。此外，该模型的增强的敏感性允许在典型的人类暴露水平的低剂量下对试剂进行测试。拟议的商业应用：将进一步开发体内转基因小鼠模型，以测试药物、环境化学品、饮食成分和紫外线的致癌潜力。由于该模型极其敏感，可以在低剂量下测试化学物质，与人类接触的水平相当。

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.