Journal article
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- Kappa B
Toxicological sciences, Vol.81(1), pp.35-42
09/01/2004
DOI: 10.1093/toxsci/kfh193
PMID: 15201435
Abstract
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- Kappa B) activation and increased hepatocyte proliferation in PCB-treated rats. In this study, the role of NF- Kappa B in hepatocyte proliferation and apoptosis after PCB administration was analyzed in wild-type mice and in mice deficient in the NF- Kappa B p50 subunit (p50 super(-/-)). In a 2- day study, mice received a single intraperitoneal (ip) injection of corn oil or PCB-153. Hepatic NF- Kappa B DNA binding activity and cell proliferation were increased by PCB-153 in wild-type mice but not in p50 super(-/-) 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- Kappa B DNA binding activity was not increased after PCB-153 treatment in wild- type or p50 super(-/-) mice. Cell proliferation was significantly increased in the wild-type mice treated with PCB-153; in the p50 super(-/-) 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 super(-/-) mice showed greater apoptosis than those of wild-type mice; PCB-153 decreased apoptosis in p50 super(-/-) 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- Kappa B p50 subunit alters the proliferative and apoptotic changes in mouse liver in the response to PCB-153.
Details
- Title: Subtitle
- 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- Kappa B
- Creators
- Zijing LuEun Y LeeLarry W RobertsonHoward P GlauertBrett T Spear
- Resource Type
- Journal article
- Publication Details
- Toxicological sciences, Vol.81(1), pp.35-42
- DOI
- 10.1093/toxsci/kfh193
- PMID
- 15201435
- ISSN
- 1096-6080
- eISSN
- 1096-0929
- Language
- English
- Date published
- 09/01/2004
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002402502771
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