US EPA

3858973 

Technical Report 

Molecular Anatomy of PFDA Hepatotoxicity as Studied by Two-Dimensional Electrophoresis 

Indiana University :: Indiana University 

1991 

16 

English 

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Perfluoro-n-decanoic acid (PFDA) effects on protein expression in the rat liver were studied in rodents following in vivo exposure to PFDA levels above, below and at the LD-50. Two-dimensional whole-liver homogenate protein patterns were generated and compared to previous results. As before, numerous proteins were altered; some suppressed, some induced, but most were unaffected. In an effort to identify the altered proteins, further analysis off basic proteins by first-dimension NEPHGE revealed the induction of cytochrome P452 (lauric acid ω-oxidase) and enoyl-CoA hydratase. Induction of these and related enzymes confirms previously observed PFDA-induced peroxisome proliferation and lends strong support to the notion that PFDA blocks normal β- oxidation, causes fatty acid accumulation, and results in compensatory peroxisomal and mitochondrial ω- and β-oxidation. Continued identification of other altered proteins will be undertaken to add to the metabolic paths affected by PFDA to further delineate its toxic mechanism. 

Accumulation; Fatty acids; Metabolism; Molecules; Proteins; Toxic agents; Perfluoro-n-decanoic acid; Hepatotoxicity; Two-dimensional electrophoresis; Cytochromes; Liver enzymes 

ADA232958