Summary (1995-2000)

The goals of this program are to investigate the effects and underlying mechanisms of action of specific toxic exposures, namely exposures to complex mixtures of hazardous substances. Once understood, such information will be used in the development of methods to detect and elucidate such effects and mechanisms of action in exposed human and nonhuman populations. The program consists of eight projects (seven biomedical and one nonbiomedical) and two cores (administration and laboratory).

Three of the biomedical projects in this program investigate the etiological factors in human breast cancer. Breast cancer risk and exposure to tetrachloroethylene (also called perchloroethylene or PCE) in drinking water is the focus of one project which entails a population-based case-control study in the Upper Cape region of Massachusetts. Another project consists of a nested case-control study of Danish women and is comparing serum concentrations of specific PCB (polychlorinated biphenyl) congeners in breast cancer cases and controls. A third project will use a geographic information system (GIS) to analyze geographically related exposures in a major case-control breast cancer study.

The other biomedical projects deal with the mechanisms and pathways by which certain classes of xenobiotics induce transcription of specific cytochrome P450 genes. Important areas of inquiry being investigated by these projects include research focussing on how xenobiotics affect metabolism, signal transduction pathways, other receptor systems, and resistance or sensitivity of species. The goal of another closely related biomedical project is aimed at developing both biological indicators and molecular markers for xenobiotic effects of spermatogenesis using cadmium as a model compound.

In the nonbiomedical project, researchers are exploring the use of sentinel species to evaluate the toxicity of ground water pollutants at a Superfund site. The study focuses on four fresh water ponds, which due to their location (at the Otis Air Force Superfund site), represent a gradient in terms of potential toxicity. Three sentinel species [a fresh water mussel, Anondonta cygnea, (a benthic species), the brown bullhead catfish, Ictalurus nebulosus, (a bottom dweller), and the painted turtle, Crysemys picta, (a pelagic species that overwinters in the sediment)] are being examined to determine toxin levels, to verify the toxicity and identity of the putative chemical agents, to assess hepatic effects, and to establish what biological effects are correlated with P450 and vitellogenin biomarkers, using endocrine/reproductive parameters.

The program is supported by an administrative core and a laboratory core. Odense University (Denmark), Woods Hole Oceanographic Institution, the University of Copenhagen, CSIRO - Australia, the University of Massachusetts, the Center for Disease Control and Prevention and the Cadmus Group, Inc. are collaborating on the research efforts of this program.