Perfluorinated Alkyl Acids in Hawaiian Cetaceans and Potential Biomarkers of Effect: Peroxisome Proliferator-Activated Receptor Alpha and Cytochrome P450 4A.

Perfluorinated alkyl acids (PFAAs) are persistent in marine biota and are toxic to many species, including marine mammals. We measured the concentrations of 15 PFAAs in liver and kidney samples of 16 species of stranded cetaceans from Hawai'i and other tropical North Pacific regions utilizing high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eleven PFAAs in liver and nine PFAAs in kidney were detected, including substantial perfluorooctanesulfonate (PFOS) and perfluoroundecanoic acid (PFUnA). Regression models indicated that phylogenetic family and age class significantly influenced concentrations of certain PFAAs. PFAAs can activate transcription factor peroxisome proliferator-activated receptor alpha (PPARα), which induces transcription of cytochrome P450 4A (CYP4A). Relative expression of PPARα and CYP4A mRNA was quantified using real-time PCR (qPCR) and CYP4A protein expression, using Western blot and then compared to PFAA concentrations in liver and kidney. Concentrations of four PFAA congeners, summation of perfluoroalkyl carboxylic acids (ΣPFCAs), and ΣPFAAs correlated significantly with PPARα mRNA expression and CYP4A protein expression in kidney, suggesting either may be biomarkers of PFAA exposure in cetaceans. This is the first study to quantify PFAAs in marine mammals from this region and the first observation of a direct relationship between PFAA exposure and PPARα and CYP4A expression in cetaceans.