Immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxylase.
Mouse strains with different susceptibility to aryl hydrocarbon hydroxylase (AHH) induction and with different levels and/or affinity for a specific cytosolic binding protein ("receptor") were used to investigate the immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Humoral antibody production was strongly inhibited in C57Bl/6 and C3H/HeN mice (more susceptible strains) with very low, single doses of TCDD (1.2 micrograms/kg), while other strains (DBA/2 and AKR) required higher doses (at least 6 micrograms/kg) to be partially suppressed. Longer exposure (8 weeks) did not increase the sensitivity of DBA/2 mice. A good correlation between the degree of enzyme inducibility and immunosuppression was observed in studies with B6D2F1 mice and backcrosses. Similar results were obtained with 2,3,7,8-tetrachlorodibenzofuran (TCDF), the most powerful competitor for TCDD "receptor" in vitro and in vivo. TCDD immunotoxic effects appeared to be associated with the presence of a specific cytosolic binding protein which mediates AHH induction.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D003433:Crosses, Genetic; D004147:Dioxins / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013045:Species Specificity
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D001189:Aryl Hydrocarbon Hydroxylases