Peroxisome proliferator-activated receptors (PPARS) and carcinogenesis

Peroxisome proliferators (PPs) are an important group of chemicals that include certain hypolipidemic drugs, plasticizers and pollutants. Many of these agents are known rodent liver tumor promoters and debate exists as to whether humans are at increased cancer risk following exposure to PPs. Research over the last decade has focused on determining the biochemical and molecular mechanisms by which peroxisome proliferators exert their effects, in the hope that this controversy will be settled. PPs regulate gene expression via a steroid hormone receptor, the peroxisome proliferator-activated receptor (PPAR). At least three subtypes of PPAR (alpha, beta and gamma) have been cloned from several species, including humans. These receptors have been implicated in tumor promotion, cellular differentiation, and apoptosis. In the present article, the current understanding of how PPARs are involved in tumorigenesis, and what this may mean to human risk assessment, will be discussed.