Abstract

Continued exposure to certain hypolipidemic drugs, plasticizers and herbicides leads to proliferation of peroxisomes in hepatic parenchymal cells. Sustained induction of peroxisome proliferation leads to the development of liver tumors in rats and mice. Peroxisome proliferator-induced pleiotropic responses, including the development of phenotypic properties in liver tumors induced by these agents, have been examined using autoradiography, immunofluorescence, immunoperoxidase, immunoelectron microscopy andin situ hybridization procedures in conjunction with northern blot and immunoblotting procedures. These studies confirmed that the biological effects of peroxisome proliferators were confined predominantly to liver cells and that the tumors appeared only in this organ. The cell specific effects of peroxisome proliferators have been documented in studies on the induction of peroxisome proliferationin vitro in primary liver cell cultures, in hepatocytes transplanted in subcutaneous fat or the anterior chamber of the eye in rats, and in rats with transdifferentiated pancreatic hepatocytes of the copper-deficiency model.

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