Abstract:
:Polychlorinatedbiphenyls (PCBs) are a group of persistent and widely dispersed environmental pollutants, some of which may be immunotoxic. In the present study, we investigated the effect of PCBs on immune system by assessing apoptotic cell death in human monocytic U937 cells. Among the various congeners tested, 2,2',4,6, 6'-pentachlorobiphenyl (PeCB), a highly ortho-substituted congener, specifically induced DNA fragmentation, a hallmark of apoptosis, while the other examined di-, tri-, tetra-, and pentachlorobiphenyls did not. To further study the 2,2',4,6,6'-PeCB-induced cell death, various features of apoptosis were examined. 2,2',4,6,6'-PeCB caused a decrease in cell viability and induced cellular morphologic features characteristic of 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-induced apoptosis. In contrast, 3,3',4,4',5-PeCB, a congener of coplanar structure, as well as 2,3,7,8-TCDD did not induce apoptosis in these human monocytic 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 apoptosis in human monocytic cells through a mechanism that is independent of the arylhydrocarbon receptor. This suggests a possibly separate mechanism by which PCBs cause immunosuppression.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Shin KJ,Bae SS,Hwang YA,Seo JK,Ryu SH,Suh PGdoi
10.1006/taap.2000.9034subject
Has Abstractpub_date
2000-11-15 00:00:00pages
1-7issue
1eissn
0041-008Xissn
1096-0333pii
S0041-008X(00)99034-3journal_volume
169pub_type
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