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

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 Pharmacol

authors

Shin KJ,Bae SS,Hwang YA,Seo JK,Ryu SH,Suh PG

doi

10.1006/taap.2000.9034

subject

Has Abstract

pub_date

2000-11-15 00:00:00

pages

1-7

issue

1

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(00)99034-3

journal_volume

169

pub_type

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