Superfund Research Program
Mechanisms of Toxic Chemical Interaction in the Liver: Interactive Hepatoxicity
Project Leader: Ruth E. Billings
Grant Number: P42ES005949
Funding Period: 1995 - 2000
Project Summary (1995-2000)
This project utilizes chemical mixtures which consist of metals (e.g. lead, chromium, and arsenic) and organics (e.g. benzene and phenol) to explore interactions in the induction of stress response proteins such as metallothionein, heme oxygenase, and nitric oxide synthase, and the induction of inflammatory cytokines (i.e. tumor necrosis factor , interleukin-1, and interleukin-6). The studies are being conducted with primary cultures of rat liver hepatoctyes. The hypothesis to be investigated is that induction of the stress response genes will influence the toxicity of components in a mixture and can be used as sensitive indicators of chemical exposure. Single chemicals as well as various combinations of chemicals are being studied in both a "top-down" and a "bottom-up" approach. The data generated in this project is being used in Project 1 for mathematical modeling by Response Surface Methodology.