Differential activation of hepatic NF-kappa B in rats and hamsters by the peroxisome proliferators Wy-14,643, gemfibrozil, and dibutyl phthalate

Nuclear factor-kappaB (NF-kappaB) is an oxidative stress-activated transcri ption factor involved in the regulation of cell proliferation and apoptosis . We found previously that the peroxisome proliferator ciprofibrate activat es NF-kappaB in the livers of rats and mice. These species are sensitive to the hepatocarcinogenic effects of peroxisome proliferators, whereas other species such as Syrian hamsters are not. In the present study we examined t he effects of 3 different peroxisome proliferators on NF-kappaB activation in rats and Syrian hamsters, The peroxisome proliferators Wy-14,643, gemfib rozil, and dibutyl phthalate were administered to animals for 6, 34, or 90 days. NF-kappaB activity was determined using electrophoretic mobility-shif t assays and confirmed using supershift assays. Wy-14,643 increased the DNA binding activity of NF-kappaB at all 3 time points in rats and produced th e highest activation of the 3 chemicals tested. Gemfibrozil and dibutyl pht halate increased NF-kappaB activation to a Lesser extent in rats and not at all times. There were no differences in hepatic NF-kappaB levels between c ontrol hamsters and hamsters treated with any of the peroxisome proliferato rs. This study demonstrates species-specific differences in hepatic NF-kapp aB activation by peroxisome proliferators.