Gene Profiling in the Livers of Wild-type and PPARα-Null Mice Exposed to Perfluorooctanoic Acid

Health concerns have been raised because perfluorooctanoic acid (PFOA) is commonly found in the environment and can be detected in humans. In rodents, PFOA is a carcinogen and a developmental toxicant. PFOA is a peroxisome proliferator-activated receptor α (PPARα) activator; however, PFOA is capable of inducing heptomegaly in the PPARα-null mouse. To study the mechanism associated with PFOA toxicity, wild-type and PPARα-null mice were orally dosed for 7 days with PFOA (1 or 3 mg/kg) or the PPARα agonist Wy14,643 (50 mg/kg). Gene expression was evaluated using commercial microarrays. In wild-type mice, PFOA and Wy14,643 induced changes consistent with activation of PPARα. PFOA-treated wild-type mice deviated from Wy14,643-exposed mice with respect to genes involved in xenobiotic metabolism. In PFOA-treated null mice, changes were observed in transcripts related to fatty acid metabolism, inflammation, xenobiotic metabolism, and cell cycle regulation. Hence, a component of the PFOA response was found to be i...