Genomic and genetic analysis of liver and kidney toxicity of trichloroethylene
Project 2 Leader: Ivan Rusyn, Texas A&M University
The need to account for genetic differences among humans in cancer susceptibility and risk assessment is becoming ever more evident to both the scientific community and regulatory agencies. Dr. Rusyn’s lab uses Trichloroethylene (TCE), a man-made, industrial chemical that has become one of the nation’s most prevalent groundwater pollutants, as a model environmental contaminant that individuals may respond to differently after exposure, but for which genetic factors are not being fully considered in risk assessment.
Dr. Rusyn will also dissect the complex mechanisms of action of an environmental agent by constructing a population-wide physiologically based pharmacokinetic (PBPK) model for TCE metabolism, which will account for inter-individual variability in metabolism from the genetics point of view by using the time-course and dose-response data obtained from the genetically-diverse mice. His team will determine the effects of inter-individual genetic variability on strain-specific responses to TCE through dose-response modeling of gene expression and metabolomics data. Collectively, this project is timely in proposing a paradigm that will not only offer valuable insights into the molecular basis for genetically-determined variability in response to TCE, but also will provide necessary science-based underpinnings and tools for the new paradigms being incorporated into the risk assessment and decision-making on TCE and related chlorinated solvents, as well as other environmental agents.