2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity.
The selective toxicity of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) for the thymus, consisting primarily of immature T-cells, led us to search for an analogous selective toxicity for the immature B-lymphocytes in the bone marrow. In the dose-response study C57B1/6 male mice were injected with either vehicle alone (corn oil), 30, 60, or 120 micrograms/kg of TCDD i.p. The mice were killed by cervical dislocation 7 days later. In the time-response study, mice were injected with either saline or 120 micrograms/kg i.p. TCDD, 3, 7, 14, or 21 days before killing. In both studies, the following were analyzed: change in body weight, thymus weight, spleen and bone marrow cellularity, and spleen and marrow B-lymphocyte function, measured using the in vitro B-lymphocyte colony forming unit in culture assay, with the mitogen lipopolysaccharide (LPS) from Salmonella typhosa, and the in vitro plaque forming cell assay, with the thymus independent antigen, TNP-LPS. In the dose-response study there was a reduction in thymic weight, spleen B-cell functional response (per spleen), and bone marrow B-cell functional response to 14%, 35-54%, and 20-32% of control, respectively, at a dosage of 120 micrograms/kg. In the time-response study, thymic weight and bone marrow B-cell functional response (per femur) were reduced to 6% and 18% of control, respectively, at day 21. The results indicate that TCDD was selectively more toxic to the immature B-cells in the bone marrow than the more mature B-cells in the spleen. This immunotoxicity was dose-dependent.
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D003114:Colony-Forming Units Assay; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006462:Hemolytic Plaque Technique; D007107:Immune System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects; D013997:Time Factors
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins