Role of Kupffer cells and oxidants in signaling peroxisome proliferator-induced hepatocyte proliferation.

There is widespread human exposure to peroxisome proliferators, which are structurally diverse compounds. Peroxisome proliferators received their name based on their ability to induce proliferation of w x peroxisomes in rodent hepatocytes 1 ; they include hypolipidemic drugs, phthalates, steroids, herbicides, w x and solvents 2 . Despite their structural diversity, these compounds induce predictable pleiotropic responses in rats and mice consisting of hepatomegaly, induction of peroxisomal enzymes of fatty acid boxidation, and an increase in both the number and w x size of peroxisomes 1 . Hepatomegaly has been attributed to hypertrophy of hepatocytes as well as w x hepatocellular hyperplasia 3 . Importantly, continu-