Polychlorinated biphenyl immunotoxicity: Dependence on isomer planarity and the Ah gene complex

Properties of certain halogenated aromatic hydrocarbons, such as cytosolic receptor binding, aryl hydrocarbon hydroxylase and cytochrome P-450 induction, and thymic atrophy, segregate with the Ah (aromatic hydrocarbon) gene complex in mice. This study tested the hypothesis that polychlorinated biphenyl (PCB) immunotoxicity in mice also segregates with the Ah gene complex and is dependent on the planarity of the PCB molecule. Male C57 BL 6 (Ah +) and DBA 2 (Ah −) mice were administered planar 3,4,3′,4′-tetrachlorobiphenyl (TCB) or nonplanar 2,5,2′,5′-TCB at doses of either 0, 10, or 100 mg/kg ip in corn oil 2 days prior to and 2 days after iv immunization with sheep erythrocytes (SRBC). Five days after immunization the primary antibody response was evaluated by the Jerne plaque assay. 3,4,3′,4′-TCB significantly decreased the number of anti-SRBC antibody-forming cells per 10 6 spleen cells and per spleen by 79 and 90%, respectively, from control values. This isomer also caused thymic atrphy, hepatomegaly, hepatic centrilobular hypertrophy, and extensive hepatic fatty infiltration; decreased body and relative spleen/body weights; and induced cytochrome P-450. These effects were observed in C57 BL 6 but not in DBA 2 mice. 2,5,2′,5′-TCB did not produce any of these effects in either strain. These results are consistent with our hypothesis and suggest that PCB immunotoxicity is mediated through a genetically controlled cytosolic receptor present in C57 BL 6 but not in DBA 2 mice and that the immunotoxic potential of PCB isomers is dependent on their conformational planarity.