Summary (2000-2005)

The major theme of the Duke University Superfund Basic Research Program, which began in 2000, is the elucidation of mechanisms of exposure and toxicity in humans and ecosystems to selected Superfund chemicals having reproductive and developmental effects. This program consists of five research projects (3 biomedical, 2 non-biomedical), one research support core (transgenic fish), and administrative, training and outreach cores. This tightly integrated program uses mammalian and fish models to elucidate mechanisms of reproductive and developmental toxicity of selected chemicals occurring at Superfund sites, with special emphasis placed on mechanisms pertaining to cellular signaling and receptor interactions involved in vertebrate development. The first of the biomedical projects focuses on the effect of chlorpyrifos on brain development, using both rat and zebrafish models. A second project is focused on developmental toxicology and the role of reactive oxygen species induced by chemical exposure to affect signaling pathways. Chemicals of interest are metals and chlorinated pesticides. The development of transgenic fish as biosensors is the theme of the third biomedical project. Researchers are using transgenic fish to study the effects of pesticides upon expression of transgenic reporter genes that indicate changes in estrogen responsive pathways and retinoic acid responsive pathways, and how these pathways affect the development of the nervous system. The two non-biomedical projects integrate with the theme of the program. A common estuarine fish, the killifish, is being used to develop a biomarker-based strategy for ecological risk assessments that assesses exposures to and reproductive/developmental effects of selected Superfund chemicals, singly or in combination. The fate and transport of chemicals studied in this program is the focus of the second non-biomedical research project. The approach combines field site evaluations with laboratory-based column studies to estimate physico-chemical properties and develop mathematical models.