HALOGENATED AROMATIC HYDROCARBON-INDUCED SUPPRESSION OF THE PLAQUE-FORMING CELL RESPONSE IN B6C3F1 SPLENOCYTES CULTURED WITH ALLOGENIC MOUSE SERUM - AH RECEPTOR STRUCTURE-ACTIVITY-RELATIONSHIPS

The immunsuppressive effects of halogenated aromatic hydrocarbons (HAH s) were investigated in B6C3F1 female mice and in mouse splenocytes cu ltured with allogenic mouse serum using the Mishell-Dutton model for i n vitro immunization to trinitrophenyl-lipopolysaccharide (TNP-LPS). E xposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-penta chlorodibenzofuran (PeCDF), 1,2,3,7,8-PeCDF, 1,3,6,8-tetrachlorodibenz ofuran (TCDF), 3,3',4,4',5-pentachlorobiphenyl (pentaCB), or 3,3 1,4,4 ',5,5'-hexaCB resulted in a dose-dependent suppression of the splenic plaque-forming cell (PFC) response both in vivo and in vitro. The effe ctive dose required to decrease 50% (ED(50)) of the response to 2,3,7, 8-TCDD, 2,3,4,7,8-PeCDF, 1,2,3,7,8-PeCDF, 1,3,6,8-TCDF, 3,3',4,4',5-pe ntaCB, or 3,3',4,4',5,5'-hexaCB in vivo was 14.1, 5.5, 1695, 34 800, 2 1, and 19 nmol/kg, respectively, and in vitro was 7.0, 10.6, 149, 2325 , 9.1 and 9.1 nM, respectively. There was an excellent rank order and linear correlation between the in vivo versus in vitro activities for these HAHs (r < 0.99) and the relative immunosuppressive potencies of these compounds paralleled their binding affinities for the aryl hydro carbon (Ah) receptor. These results show that splenocytes cultured wit h allogenic mouse serum is an Ah-responsive in vitro assay which can b e used for quantitating the immunosuppressive effects of HAHS.