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Toxicity of Peroxisome Proliferators

Molecular and Cellular Aspects of Toxicology

  1. John P. Vanden Heuvel PhD

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat023

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Vanden Heuvel, J. P. 2009. Toxicity of Peroxisome Proliferators. General, Applied and Systems Toxicology. .

Author Information

  1. Penn State University, Center for Molecular Toxicology and Department of Veterinary and Biomedical Sciences, Pennsylvania, USA

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Peroxisome proliferators (PPs) are an important group of chemicals that include certain hypolipidemic drugs, plasticizers and pollutants. Chemicals that are classified as PPs are known rodent liver tumor promoters, although there is debate whether humans are at increased cancer risk upon exposure. The effects observed upon long-term treatment of rodents to PPs include hepatic peroxisome proliferation, hepatomegaly, regulation of gene expression, alteration in cell cycle control and ultimately, carcinogenesis. The majority of the physiological, toxicological and carcinogenic effects induced by PPs are mediated by a nuclear hormone receptor, Peroxisome Proliferator-Activated Receptor-α (PPARα). Although humans respond to PPs via PPARα activation resulting in altered lipid metabolism, there is little evidence for peroxisome proliferation or liver cancer. In the present chapter, the current understanding of how PPARs are involved in tumorigenesis, and what this may mean to human risk assessment, will be discussed.

Keywords:

  • peroxisome;
  • peroxisome proliferator;
  • nuclear hormone receptor;
  • PPAR;
  • gene expression;
  • oxidative stress;
  • knock-out mice;
  • carcinogenesis;
  • toxicology