Peroxisome proliferators: a model for receptor mediated carcinogenesis

Abstract

Peroxisome proliferators are a diverse group of rodent hepatocarcinogens, which include hypolipidaemic drugs, plasticizers and herbicides. A member of the nuclear hormone receptor superfamily has been identified that can be activated by peroxisome proliferators. The receptor is therefore termed the peroxisome proliferator activated receptor (PPAR). Three Xenopus nuclear hormone receptors have been described that are closely related to the mouse PPAR and can all be activated by peroxisome proliferators. Therefore, a family of PPARs that is possibly important in mediating the action of some hypolipidaemic drugs may exist in many species including mice and humans. The most widely used marker of peroxisome proliferator action is the peroxisomal beta-oxidation enzyme acyl CoA oxidase. PPAR recognizes a specific peroxisome proliferator response element located in the acyl CoA oxidase gene promoter. It is therefore argued that the hypolipidaemic and carcinogenic effects of peroxisome proliferators may be mediated by PPAR in a manner similar to that of steroid hormone action.