The investigators have shown that prenatal exposure to the polychlorinated hydrocarbon pesticide, chlordane, affects the normal immune ontogeny. They recently found that these prenatally-exposed animals have a severe reduction in the ability of stem cells in the fetal liver, and in 100 and 200 day old bone marrow, to respond to granulocyte/macrophage-colony stimulating factor (GM-CSF) and to recolonize the spleens of irradiated animals (CFU-S) indicating that chlordane may be permanently affecting stem cells during ontogeny. Research is proposed to identify the stage in ontogeny initially affected, i.e., does chlordane have its effect as the pluripotent stem cell prior to its differentiation into a committed progenitor cell, determine the cell cycle stage affected by the chlordane in the target stem cell, and based on this information investigate the mechanistic causes of the defect(s). A goal is to more extensively define the model by determining the timing of the chlordane effects during gestation; determining the fetal-maternal tissue(s) affected by the chlordane; and determining whether the defect can be passed to the progeny (F2) of the affected F1 generation. A functional deficit in macrophages could account for previous reported decreases in DTH, or the consequences of a reduced DTH, as the macrophage plays a large role in the efferent phase of DTH reaction. A plan therefore is to thoroughly examine the macrophage for possible defects by examining the activation pathway of the macrophage at 100 days of age to determine the stage affected, and determine the intracellular location and nature of the defect by examining immunological, biochemical and molecular biological techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES002875-10
Application #
2153209
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1982-06-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1995-03-31
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost
Name
West Virginia University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
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