Immunotoxicity of the halogenated aromatic hydrocarbons-QSARs and interactive effects
The role of the aryl hydrocarbon (Ah) receptor in mediating the immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and related halogenated aromatic hydrocarbons (HAHs) on the murine splenic plaque-forming cell (PFC) response to the T-cell dependent antigen, sheep red blood cell (SRBC), was investigated. Both the in vivo and in vitro (Mishell-Dutton) models for this immunotoxic response were utilized in these studies. The in vivo structure-immunotoxicity relationships for a series of five polychlorinated dibenzofurans (PCDFS) and seven polychlorinated biphenyls (PCBs) were evaluated in C57BL/6 (Ah-responsive) mice and the results showed that there was a good correlation with previous structure activity relationship studies for other putative Ah receptor-mediated responses. In addition, the partial antagonism of 2,3,7,8-TCDD-induced suppression of the in vivo PFC response by 1,3,6,8-TCDF, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF), several commercial PCB mixtures, and the selected PCB congeners was observed in C57BL/6 mice and these data also support a receptor-mediated mechanism of action. Studies utilizing spleen cell cultures from both C57BL/6 (Ah-responsive) and DBA/2 (Ah-nonresponsive) mice for the splenic PFC response to SRBCs did not support an Ah receptor-mediated mechanism of action for HAH-induced immunosuppression. The same series of PCDF congeners which were investigated in vivo were also evaluated in the in vitro model and the data showed an absence of a structure dependent immunosuppression by the PCDFs. These results contrasted with those obtained the in vivo studies and suggested the mode of action was independent of the Ah receptor protein. Studies on the partial antagonism of 2,3,7,8-TCDD-induced immunosuppression by 2,2{prime},4,4{prime},5,5{prime}-HCBP and {alpha}-naphthoflavone did not support a receptor-mediated mechanism of action for the in vitro model.
- Research Organization:
- Texas A and M Univ., College Station, TX (USA)
- OSTI ID:
- 6409708
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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CHLORINATED AROMATIC HYDROCARBONS
TOXICITY
DIOXIN
ERYTHROCYTES
IMMUNOSUPPRESSION
IN VITRO
IN VIVO
MICE
RECEPTORS
SHEEP
SPLEEN CELLS
STRUCTURE-ACTIVITY RELATIONSHIPS
ANIMAL CELLS
ANIMALS
AROMATICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
DOMESTIC ANIMALS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PROTEINS
RODENTS
RUMINANTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology