title: Effect of vitamin E on hepatic cell proliferation and apoptosis in mice deficient in the p50 subunit of NF-κB after treatment with phenobarbital.
abstract: Phenobarbital (PB) is an efficacious and well-studied hepatic tumor promoting agent. Nuclear factor-κB (NF-κB) is a transcription factor activated by reactive oxygen and is involved in cell proliferation and apoptosis. We previously found that PB activates NF-κB and that dietary vitamin E is effective in decreasing PB-induced NF-κB DNA binding. We therefore hypothesized that dietary vitamin E influences PB-induced changes in cell proliferation and apoptosis through its action on NF-κB. NF-κB1 deficient mice (p50-/-) and wild-type B6129 mice were fed a purified diet containing 10 or 250ppm vitamin E (α-tocopherol acetate) for 28days. At that time, half of the wild-type and half of the p50-/- mice were placed on the same diet with 0.05% PB for 10days. Compared to wild-type mice, the p50-/- mice had higher levels of cell proliferation and apoptosis. Cell proliferation was significantly increased by PB, but vitamin E did not affect hepatic cell proliferation. Apoptosis was not changed in mice fed PB, and there was no significant difference in apoptosis between control and high vitamin E treated mice. Thus, vitamin E does not appear to influence cell growth parameters in either wild-type or p50-/- mice.
authors: Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40506, United States.
authors: Jun
authors: J
authors: Li
authors: Casey
authors: C
authors: Harp
authors: Job C
authors: JC
authors: Tharappel
authors: Brett T
authors: BT
authors: Spear
authors: Howard P
authors: HP
authors: Glauert
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000172:deficiency* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D052002:NF-kappa B p50 Subunit; D014810:Vitamin E; D010634:Phenobarbital