2,2',4,6,6'-pentachlorobiphenyl induces apoptosis in human monocytic cells.
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.
Shin
K J
KJ
School of Environmental Engineering, Pohang University of Science and Technology, Pohang, 790-784 Kyungbuk, Republic of Korea.
Bae
S S
SS
Hwang
Y A
YA
Seo
J K
JK
Ryu
S H
SH
Suh
P G
PG
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002467:Cell Nucleus / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D008113:Liver Neoplasms; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014343:Trypan Blue / Q000378:metabolism; D020298:U937 Cells / Q000166:cytology / Q000187:drug effects
D004396:Coloring Agents; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013778:Tetrazolium Salts; D013844:Thiazoles; D004247:DNA; D011078:Polychlorinated Biphenyls; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue; D014343:Trypan Blue; C417207:2,2',4,6,6'-pentachlorobiphenyl