STUDY OF THE SEPARATE AND COMBINED EFFECTS OF THE NONPLANAR 2,5,2',5'-TETRACHLOROBIPHENYL AND THE PLANAR 3,4,3',4'-TETRACHLOROBIPHENYL IN LIVER AND LYMPHOCYTES INVIVO

Polychlorinated biphenyls (PCBs) are a group of industrial chemicals that are widely distributed in the environment. Because these compounds occur as mixtures, studies of their possible interactive effects are essential for an understanding of the mechanism of the toxicity of these mixtures. For the determination of a possible interaction of the effects in vivo of 2,5,2',5'-tetrachlorobiphenyl (TCB) and 3,4,3',4'-TCB, rats were exposed to a single dose of diethylnitrosamine (DEN) and subsequently to 0.1 p.p.m. 3,4,3',4'-TCB and/or 10 p.p.m. 2,5,2',5'-TCB in the feed for 1 year. The two major targets of PCB toxicity, the liver and the peripheral blood, were examined after these treatments. TCB treatment after DEN exposure caused a predominance of increased placental glutathione S-transferase (PGST) and deficiencies of ATPase as preneoplastic markers in focal hepatic lesions. When 0.05% phenobarbital (PB) was administered after DEN exposure, the distribution of markers in altered hepatic foci (AHF) was essentially equal for increased PGST and gamma-glutamyltranspeptidase (GGT) and for ATPase deficiency. Many of these AHF also exhibited increased P450 b/e expression. Our results demonstrated that the two PCB congeners interacted in vivo to produce an increase in AHF that were PGST positive and ATPase negative. PGST-positive and ATPase-negative AHF correlated best with focal areas of P450 b/e expression. The combination of the two PCBs caused a greater than additive decrease in the total number of lymphocytes and antibody-producing B-cells. Also the thymocyte-dependent T-helper cells isolated from the animals receiving the combination of TCBs demonstrated a morphologically abnormal subpopulation. The results indicate that the interaction of 2,5,2',5'-TCB and 3,4,3',4'-TCB in vivo induced much greater toxicity and mutagenicity in peripheral lympyhocytes and hepatocytes than treatment with either congener alone.