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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
Project #
Application #
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arkansas for Medical Sciences
Schools of Medicine
Little Rock
United States
Zip Code
Blyler, G; Landreth, K S; Barnett, J B (1994) Gender-specific effects of prenatal chlordane exposure on myeloid cell development. Fundam Appl Toxicol 23:188-93
Theus, S A; Tabor, D R; Soderberg, L S et al. (1992) Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure. Agents Actions 37:140-6
Theus, S A; Lau, K A; Tabor, D R et al. (1992) In vivo prenatal chlordane exposure induces development of endogenous inflammatory macrophages. J Leukoc Biol 51:366-72
Blaylock, B L; Soderberg, L S; Gandy, J et al. (1990) Cytotoxic T-lymphocyte and NK responses in mice treated prenatally with chlordane. Toxicol Lett 51:41-9
Barnett, J B; Blaylock, B L; Gandy, J et al. (1990) Long-term alteration of adult bone marrow colony formation by prenatal chlordane exposure. Fundam Appl Toxicol 14:688-95
Barnett, J B; Blaylock, B L; Gandy, J et al. (1990) Alteration of fetal liver colony formation by prenatal chlordane exposure. Fundam Appl Toxicol 15:820-2
Beggs, M; Menna, J H; Barnett, J B (1985) Effect of chlordane on influenza type A virus and herpes simplex type 1 virus replication in vitro. J Toxicol Environ Health 16:173-88
Menna, J H; Barnett, J B; Soderberg, L S (1985) Influenza type A virus infection of mice exposed in utero to chlordane;survival and antibody studies. Toxicol Lett 24:45-52
Barnett, J B; Holcomb, D; Menna, J H et al. (1985) The effect of prenatal chlordane exposure on specific anti-influenza cell-mediated immunity. Toxicol Lett 25:229-38