In this review, the role of NF-kappaB in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-kappaB in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-alpha (PPARalpha) activation in non-hepatic tissues can lead to the inhibition of NF-kappaB activation. Several lines of evidence support the hypothesis that the activation of NF-kappaB by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-kappaB in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-kappaB knockout models. Specifically, the induction of cell proliferation and the promotion of liver carcinogenesis are inhibited in mice lacking the p50 subunit of NF-kappaB. Overall, the activation of NF-kappaB appears to be important in the carcinogenic activity of peroxisome proliferators.

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Published in PPAR Research, v. 2008, 286249.

© 2008 Howard P. Glauert et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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