Poster 12
Presenter: David Threadgill
Thursday, 4:00 – 6:00pm
David Threadgill and Michelle DeSimone Department of Genetics, North Carolina State University, Raleigh, NC 27695
Recent epidemiology data suggests that exposure to trichloroethylene (TCE) is associated with increased susceptibility to a variety of diseases including elevated incidence of kidney cancer. To investigate genetic susceptibility to TCE, we exposed a genetically diverse mouse population to two dose levels of TCE with or without two dose levels of inorganic arsenic (iAS), a toxicant naturally found in the environment and in contaminated food sources. We observed cooperation between TCE and iAS in the induction of a gene expression signature in kidneys indicative of a tumor promoted environment. After one year of exposure, subsets of mice developed kidney cancers, some of which became metastatic to the lung. The results demonstrate that these chemicals can elicit additive and synergistic toxicities in susceptible individuals. Furthermore, the target organs in the genetically heterogeneous mouse populations are similar to those in humans, indicating that susceptibility alleles in the mouse population model will inform on human susceptibility. Genetic analysis of the exposed mouse population should reveal alleles contributing to susceptibility in sensitive individuals.