Suppression of humoral antibody production by exposure to 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin.
The day 4 IgM antibody (AB) response to sheep red blood cells was suppressed in adult female B6C3F1 mice subchronically (14 day) exposed to 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (1,2,3,6,7,8-HCDD) at concentrations reflecting the levels of this dioxin isomer as a contaminant in technical-grade pentachlorophenol. Hepatic microsomal parameters were also measured in these mice and indicated the characteristic induction of mixed-function oxidase enzyme activities, particularly aryl hydrocarbon hydroxylase. The response to sheep red blood cells was also suppressed when measured in vitro by culturing the antigen with spleen cells from a second group of mice subchronically exposed to 1,2,3,6,7,8-HCDD. Enumeration studies with fluorescent-labeled antisera in these animals indicated a dose-related suppression in the number of T-lymphocytes with no effect on B-lymphocytes. 1,2,3,6,7,8-HCDD directly suppressed several in vitro AB responses when added to cultures of spleen cell suspensions from untreated B6C3F1 mice. The rank order of sensitivity was determined to be: polyclonal AB response to LPS greater than or equal to T-independent AB response to DNP-Ficoll greater than T-dependent AB response to sheep red blood cells. Subsequent studies indicated that the suppression by 1,2,3,6,7,8-HCDD could be produced after only a 30-min preincubation. The suppression of all in vitro AB responses was abolished when the dioxin was preincubated with a metabolic activation system: crude liver homogenate (B6C3F1 mice pretreated with the mixed-function oxidase inducer; Aroclor 1254) plus NADP and isocitrate. The suppression of the T-dependent AB response was still evident when the metabolic activation system was heat-inactivated (as verified by an inability to activate cyclophosphamide) prior to the preincubation.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001711:Biotransformation; D001774:Blood Chemical Analysis; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; C018073:hexachlorodibenzo-4-dioxin; D001189:Aryl Hydrocarbon Hydroxylases