Superfund Research Program

Dogs as a Model for Assessment of Immunotoxicity of Environmental Pollutants

Project Leader: Fred W. Quimby
Grant Number: P42ES005950
Funding Period: 1995 - 2000

Project-Specific Links

Final Progress Reports

Year:   1999 

Studies on the effects of PCBs on canine peripheral blood lymphocyte cultures continued with the further development of canine specific monoclonal antibodies to cytokines: tumor necrosis factor, interleukin-10, interleukin-8, interleukin-12 and interferon-gamma. These antibodies have been used in dual fluorescent staining techniques to identify CD4 positive lymphocytes of the TH1 (CD4+, IFM+) or TH2 (CD4+, IL-10+) functional subpopulations. PCB-contaminated sediment from the St. Lawrence River at Akwesasne was compared to control sediments for its ability to alter the development of larval frogs (Woodfrogs). Striking dose-related effects were seen in mortality. Non-fatal alterations in swimming and feeding behavior were also documented which correlated with the uptake of diorthochlorinated biphenyls from the water. Finally, based on observations that dogs exposed to low levels of PCB (5ppm in diet) show an alteration in the function of the hypothalamic-pituitary axis, project investigators developed an in vitro model using pituitary cell lines (GH cells) and dispersed rat anterior pituitary glands. PCBs added at low concentrations, 50-100 ppb in media, caused profound changes in TSH-induced release of prolactin from both cell types mimicking the physiologic abnormality in dogs. Molecular probes demonstrated a PCB-induced block in one MAP kinase pathway of signal transduction following TRH exposure.