Effect of 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) on hepatocyte proliferation and apoptosis in mice deficient in the p50 subunit of the transcription factor NF-κB

Zijing Lu, Eun Y. Lee, Larry W. Robertson, Howard P. Glauert, Brett T. Spear

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Polychlorinated biphenyls (PCBs) are a group of synthetic chemicals that induce and promote liver tumors in rodents. We previously showed hepatic nuclear factor kappaB (NF-κB) activation and increased hepatocyte proliferation in PCB-treated rats. In this study, the role of NF-κB in hepatocyte proliferation and apoptosis after PCB administration was analyzed in wild-type mice and in mice deficient in the NF-κB p50 subunit (p50-/-). In a 2-day study, mice received a single intraperitoneal (ip) injection of corn oil or PCB-153. Hepatic NF-κB DNA binding activity and cell proliferation were increased by PCB-153 in wild-type mice but not in p50-/- mice. In a 21-day study, mice received six ip injections of corn oil or PCB-153 (twice weekly for 3 weeks) and were euthanized 4 days after the last injection. In this study, NF-κB DNA binding activity was not increased after PCB-153 treatment in wild-type or p50-/- mice. Cell proliferation was significantly increased in the wild-type mice treated with PCB-153; in the p50-/- mice treated with PCB-153, cell proliferation was greater than in untreated mice but less than in wild-type mice treated with PCB-153. The livers of p50-/- mice showed greater apoptosis than those of wild-type mice; PCB-153 decreased apoptosis in p50-/- mice, with higher inhibition in the 21-day study than in the 2-day study. RNase protection assays indicated that PCB-153 decreased the mRNA level of cyclin A2, B1, B2, and C in the 2-day study, but not in the 21-day study; however, it did not affect cyclin D1 and D2 mRNA levels at either time point. Cyclin D1 protein levels were not affected by PCB-153. Taken together, these data indicate that the absence of the NF-κB p50 subunit alters the proliferative and apoptotic changes in mouse liver in the response to PCB-153.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalToxicological Sciences
Issue number1
StatePublished - Sep 2004

Bibliographical note

Funding Information:
We are grateful to Job Tharappel, Karen Calfee-Mason, and Petruta Bunaciu for their assistance with animal treatment and tissue collection. We thank Hans-Joachim Lehmler, of the Synthesis Core of the University of Kentucky Superfund Basic Research Program (ES07380), for chemically synthesizing the PCB-153 used in this study. This research was supported by grant ES07380 from the National Institute of Environmental Health Sciences (NIEHS) and by the Kentucky Agricultural Experiment Station. Z. Lu was supported by the Training Core of the NIEHS Superfund Basic Research Program (ES07380), by a Kentucky Opportunity Fellowship from the Graduate School of the University of Kentucky, and by a Dissertation Enhancement Award from the Graduate School of the University of Kentucky.


  • Apoptosis
  • Cell proliferation
  • Hepatocytes
  • NF-κB
  • PCBs

ASJC Scopus subject areas

  • Toxicology


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