ToxSci Advance Access published online on June 16, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh193
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506; Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506
* To whom correspondence should be addressed. E-mail: bspear{at}uky.edu.
Polychlorinated biphenyls (PCBs) are a group of synthetic chemicals that induce and promote liver tumors in rodents. We previously showed hepatic NF-
Accepted May 18, 2004
Carcinogenicity
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-
B
2 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506; Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky 40506; Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506
3 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506; Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506; Department of Nutrition and Food Science, University of Kentucky, Lexington, Kentucky 40506
4 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40506; Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky 40506; Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40506; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, Kentucky 40506
Abstract 
B activation and increased hepatocyte proliferation in PCB-treated rats. In this study, the role of NF-B in hepatocyte proliferation and apoptosis after PCB administration was analyzed in wild-type mice and mice deficient in the NF-B p50 subunit (p50-/-). In the 2-day study, mice received a single intraperitoneal (i. p.) injection of corn oil or PCB-153. Hepatic NF-B DNA binding activity and cell proliferation were increased by PCB-153 in wild-type but not in p50-/- mice. In the 21- day study, mice received six i.p. injections of corn oil or PCB-153 (twice weekly for three weeks) and were euthanized 4 days after the last injection. In this study, NF-B 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 increased compared to untreated mice but less than wild-type mice treated with PCB-153. The livers of p50-/- mice showed greater apoptosis than those in wild-type mice; PCB-153 decreased apoptosis in p50-/- mice, with the 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; but did not affect cyclin D1 and D2 mRNA levels at either timepoint. Cyclin D1 protein levels were not affected by PCB-153. Taken together, these data indicate that the absence of the NF-B p50 subunit alters the proliferative and apoptotic changes in mouse liver in the response to PCB-153.B, hepatocytes, apoptosis, cell proliferation
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