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Peroxisome proliferators: a model for receptor mediated carcinogenesis
1Imperial Chemical Industries, Central Toxicology Laboratory, Macclesfield, Cheshire.
Cancer Surveys
|January 1, 1992
Summary
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors activated by various chemicals. These PPARs may mediate the hypolipidemic and carcinogenic effects of peroxisome proliferators.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- Peroxisome proliferators are diverse chemicals known to cause liver cancer in rodents.
- These compounds include hypolipidemic drugs, plasticizers, and herbicides.
- A nuclear hormone receptor superfamily member, PPAR, has been identified, activated by peroxisome proliferators.
Purpose of the Study:
- To identify and characterize the peroxisome proliferator activated receptor (PPAR).
- To investigate the role of PPAR in mediating the effects of peroxisome proliferators.
- To explore the potential existence of a PPAR family across species.
Main Methods:
- Identification of a nuclear hormone receptor activated by peroxisome proliferators.
- Characterization of related Xenopus nuclear hormone receptors.
- Analysis of PPAR's interaction with the acyl CoA oxidase gene promoter.
Main Results:
- A nuclear hormone receptor, PPAR, was identified and activated by peroxisome proliferators.
- Three Xenopus nuclear hormone receptors related to mouse PPAR were found to be activated by peroxisome proliferators.
- PPAR was shown to recognize a specific response element in the acyl CoA oxidase gene promoter.
Conclusions:
- A family of PPARs may exist in various species, including humans.
- PPAR likely mediates the hypolipidemic and carcinogenic actions of peroxisome proliferators.
- The mechanism of action for PPAR may be analogous to steroid hormone action.