Chlordane is a chlorinated hydrocarbon pesticide commonly used for termite control for residential and commercial structures and with its extremely long half-life has become prevalent world-wide. For example, the metabolites and residues of chlordane have been shown to be present in the tissues of a number of animal species (1, 2) as well as the milk of lactating humans in the U.S. and other countries (2). Our laboratory (3-6) has reported that in utero exposure of mice to chlordane results in a dramatic depression in delayed-type hypersensitivity (DTH) and an increase in survival to influenza A/PR/8/34 virus following infection as adults. The chlordane-mediated alteration in resistance to infectious disease appears to be related to a number of immunological changes, including the DTH. The purpose of this proposal is to investigate in greater detail the immunological effects of in utero exposure to chlordane and the impact of these effects on the pathogenesis of an infectious disease which is also ubiquitous, influenza. Initially, we intend to determine the mechanism of DTH depression by in utero chlordane exposure by testing chlordane effects on the cells and soluble products of the afferent and efferent phases of DTH. We will also determine the mechanism of clearance of the virus by measuring a number of viral specific immune parameters, such as cytotoxicity and interferon. Our data suggest that chlordane may affect specific T suppressor cells, which regulate DTH and this will also be investigated. We will initiate a series of experiments designed to determine if mice, exposed to chlordane as young adults, also manifest changes in their DTH and in their ability to resist influenza infection. We will determine whether and such effects might be due to changes in the kinetics of viral replication in the lung and if immune reactions are affected in the same way as in utero chlordane treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
3R01ES002875-06S1
Application #
3250123
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1982-06-01
Project End
1991-03-31
Budget Start
1990-07-10
Budget End
1991-03-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
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