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Genetically Modified Models

The conventional rodent bioassay has been used for over three decades and is accorded credibility in identifying carcinogens thought to pose risks for human health. An ongoing goal of the NTP is to seek other model systems for toxicology and carcinogenesis studies, especially those that can provide mechanistic information relative to understanding an agent's mode of action. The use of genetically modified models holds promise for improving both the accuracy and efficacy of experimental assessment of the carcinogenic potential of chemicals. Genetically altered or "transgenic" mouse models carry activated oncogenes or inactivated tumor suppressor genes known to be involved in neoplastic processes both in humans and rodents. This trait may allow them to respond to carcinogens more quickly than conventional rodent strains. In addition, the neoplastic effects of agents can be observed in transgenic models within a time frame in which few, if any, spontaneous tumors would arise. The high incidences of spontaneous or background tumors, which occur most often late in the two-year rodent cancer studies, are among the most confounding factors for interpreting the findings of chemical carcinogenesis and their implications for human health. The use of target or reporter genes also allows for direct molecular and cellular analysis of a chemical's effects in these models and can provide additional mechanistic information about mode of action.