2,2 ',4,6,6 '-pentachlorobiphenyl induces apoptosis in human monocytic cells

Polychlorinated biphenyls (PCBs) are a group of persistent and widely dispe rsed environmental pollutants, some of which may be immunotoxic. In the pre sent study, we investigated the effect of PCBs on immune system by assessin g apoptotic cell death in human monocytic U937 cells. Among the various con geners tested, 2,2',4,6,6'-pentachlorobiphenyl (PeCB), a highly ortho-subst ituted congener, specifically induced DNA fragmentation, a hall-mark of apo ptosis, while the other examined di-, tri-, tetra-, and pentachlorobiphenyl s did not. To further study the 2,2',4,6,6'-PeCB-induced cell death, variou s features of apoptosis were examined. 2,2',4,6,6'-PeCB caused a decrease i n cell viability and induced cellular morphologic features characteristic o f apoptosis such as chromatin aggregation and apoptotic bodies. In addition , caspase-3, an executioner of apoptosis, was activated and its substrate, poly(ADP-ribose) polymerase (PARP), was cleaved during 2,2',4,6,6'-PeCB-ind uced apoptosis. In contrast, 3,3',4,4',5-PeCB, a congener of coplanar struc ture, as well as 2,3,7,8-TCDD did not induce apoptosis in these human monoc ytic cells, although they potently induced CYP 1A1 in human hepatoma Hep G2 cells. Taken together, the data indicate that 2,2',4,6,6'-PeCB induces apo ptosis in human monocytic cells through a mechanism that is independent of the arylhydrocarbon receptor. This suggests a possibly separate mechanism b y which PCBs cause immunosuppression. (C) 2000 Academic Press.