Immunosuppressive activities of polychlorinated biphenyls in C57BL/6N mice: Structure-activity relationships as Ah receptor agonists and partial antagonists

The immunosuppressive activity of polychlorinated biphenyl (PCB) congeners is structure-dependent and 2 classes of compounds, namely the coplanar (class I) and monoortho coplanar (class II) congeners exhibit immunotoxicity. This study extends the structure-immunotoxicity relationships for PCBs by investigating representative congeners from the following structural classes of PCBs: monoortho coplanar (2,3,3′,4,4′,5-hexachlorobiphenyl, class II); monoortho coplanar minus a single para-chloro group (2,3,3′4,5,5′-hexachlorobiphenyl, and 2,3,3′,4,5′-pentachlorobiphenyl, class III); diortho coplanar (2,3′,4,4′5′6-hexachlorobiphenyl, class IV); triortho coplanar (2,2′,4,4′,5,6′-hexachlorobiphenyl class V) and a tetraortho-substituted PCB (2,2′,4,4′,6,6′-hexachlorobiphenyl, class VI). The effects of these compounds on the splenic plaque forming cell response to sheep red blood cells was determined in 7-8 week old male C57BL/6N mice. The results showed that the class II-IV congeners were immunotoxic and with only one exception these compounds also induced hepatic microsomal aryl hydrocarbon hydroxylase and ethoxyresorfin O-deethylase activities and displaced [³H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from the cytosolic aryl hydrocarbon (Ah) receptor in competitive binding assays. These results thus extend the structure-activity relationships for PCBs as Ah receptor agonists. The interaction of these PCB congeners with an ED_70-90 dose of TCDD (3.7 nmol/kg) showed that only one structural class of compounds, namely class III, partially antagonized TCDD-mediated immunotoxicity.