Project Summary (2000-2006)

This project is focusing on development of sound scientific understanding of the mode of action and the observed and expected dose response relationship of several of the major hazardous chemicals on the National Priority List. These data are suitable for use with the 1996 Revised Cancer Risk Assessment Guidelines and are improving the accuracy of risk assessments. Project investigators have hypothesized that several aliphatic and aromatic chlorinated hydrocarbons share an important mode of action referred to as "oxidative stress." Through this mechanism, Reactive Oxygen Species (ROS) cause damage to DNA and activate signal transduction pathways involved in gene regulation and cell proliferation. This research is identifying the most useful biomarkers of oxidative stress and examining the extent and type of oxidative stress-related damage to DNA and proteins that are produced by NPL chemicals. These biomarkers are being examined in human blood samples of individuals with known concentrations of PCBs.