Assessment of Immunotoxicity Induced by the Environmental Chemicals 2,3,7,8-Tetrachlorodibenzo-p-dioxin, Diethylstilbestrol and Benzo(a)pyrene

Abstract

A testing battery will be described for assessing alterations in immunological function and host resistance following exposure of B6C3F1 mice to TCDD, DES and BP. TCDD is a major contaminant of the defoliant 2,4,5 T (agent orange); DES is a potent synthetic estrogen used therapeutically to prevent menopausal symptoms and post-coital implantation, and as a weight promotant in cattle; and BP is the principal carcinogen in cigarette smoke and coal tar. Mice exposed perinatally to TCDD (5, 1 μg/kg) exhibited marked thymus atrophy and depressed mitogenic responses. Resistance to Listeria monocytogenes, gram-negative endotoxin and transplantable syngeneic tumor cells were likewise impaired. The mice appeared to have a specific T-cell defect associated with a receptor for TCDD present at high levels in thymic tissue. Mice exposed to DES at 8.0, 2.0 and 0.2 mg/kg of body weight for 5 days exhibited severe thymus atrophy accompanied by depression of the following parameters: antibody PFC response to SRBC and LPS; delayed cutaneous hypersensitivity; lymphoproliferative response to T- and B-cell mitogens and alloantigens; bone marrow cellularity; and stem and granulocyte-macrophage progenitor cell proliferation. Macrophages were activated relative to phagocytic, proliferative and tumoricidal responses with evidence of suppressor cell activity. Host resistance parameters were likewise impaired. Thus, DES exposure resulted in RES stimulation, severely depressed immunological and host resistance function, due in part to macrophage suppressor cells and possibly a T-cell defect. Finally, BP was dosed at 400, 200 and 50 mg/kg of body weight over 10 days. BP exposed mice demonstrated depressed antibody PFC responses; lymphoproliferative responses to mitogens; and depressed numbers of bone marrow macrophage-granulocyte progenitors. Macrophage function and host resistance to Listeria and tumor cells were unaffected. These data demonstrate the sensitivity of the immune response for detecting selective or non-specific chemical toxicity and support the hypothesis that certain carcinogens may operate via immunological mechanisms.