Superfund Research Program
Epigenetic Effects of Pre- and Post-Remediated Environmental Toxicants
Project Leader: James E. Trosko
Grant Number: P42ES004911
Funding Period: 1995 - 2006
Project Summary (2000-2006)
The goal of this interdisciplinary project is to use an in vitro human neuron cell line with stem cell-like potential, to study the molecular, biochemical, and cellular mechanisms that might be affected by exposure to environmental toxicants prior to or after biological or chemical remediation processes. The hypothesis is that blockage of gap junctional intercellular communication (GJIC) by toxic chemicals is mediated by specific signal transduction mechanisms which alter the expression of a specific battery of genes which, in turn, could affect the cell's ability to regulate proliferation, cell differentiation or apoptosis. Results will provide validation of the inhibition of GJIC as a predictive endpoint of chemicals that can be toxic via their ability to trigger various signal transduction mechanisms that alter gene expression controlling responses of differentiated cells. In addition, by using DNA microarray technology on a human in vitro system where many confounding factors can be controlled, identification of those genes associated with chemical-induced signal transduction systems and their associated biological effects is easier and more relevant to the extrapolation of risk assessment in human beings than the use of tissues from animal systems.