Technical advances in the past decade have provided the capability to genetically manipulate the mammalian genome. A product of this technology is the development of transgenic rodents with altered expression of specific genes by either disabling a specific gene or increasing expression by random integration of a transgene or increasing gene dosage at the endogenous locus. Genetic crosses of rodents with different phenotypes and genotypes have been critical to verifying the role of activation of protooncogenes and/or loss of tumor suppressor genes in cancer. Transgenic rodent models are particularly important to defining cellular and molecular processes involved in chemical carcinogenesis. Rodent models have the inherent capability for physiological tissue distribution and metabolism of chemicals which are deficiencies of in vitro systems. Most importantly, the use of rodent models allows hypothesis based experimentation to determine, evaluate and characterize dose response curves under rigorously controlled conditions and the biological outcome. The major objective of this project is to evaluate and characterize transgenic rodent model systems for their use as surrogates to identify carcinogens that may pose significant risk to human health. This project shall involve the acquisition and receipt of specific transgenic or transgenic mutant or rodent strains from outside sources, quarantine, housing, breeding, genotyping, and maintaining the acquired rodents prior to initiating experiments. In addition, the Contractor will have the capability to house, breed, and treat animals that are not considered to be pathogen-free.
| Bushel, P R; Heinloth, A N; Li, J et al. (2007) Blood gene expression signatures predict exposure levels. Proc Natl Acad Sci U S A 104:18211-6 |
