Cellular distribution of cytochrome P-450E in winter flounder liver with degenerative and neoplastic disease

Abstract

A characteristic hepatic pathology is highly prevalent in winter flounder ( Pseudopleuronectes americanus) from Boston Harbor. Here we report initial evaluation of the cellular expression of a cytochrome P-450E analog in normal and diseased winter flounder liver using immunohistochemical analysis with MAb 1-12-3, a monoclonal antibody specific for P-450E. Cytochrome P-450E (P-450IAI) is the polynuclear aromatic hydrocarbon (PAH)- and polychlorinated biphenyl-inducible form of P-450 from scup ( Stenotomus chrysops). MAb 1-12-3 was first applied to formalin-fixed, paraffin-embedded sections of control and 3,3,4,4-tetrachlorobiphenyl-treated scup liver using an indirect peroxidase staining technique to visualize antibody binding. The results demonstrated specific positive staining of hepatocytes, bile and pancreatic duct epithelium and endothelium for P-450E, confirming utility of MAb 1-12-3 in analysis of fixed tissue. Subsequent analysis of archival winter flounder liver also demonstrated positive staining of hepatocytes. No staining of abnormally vacuolated cells was present in any of the fish; however, nodules of such cells occasionally contained islands of intensely staining cells of unknown origin. The cellular distribution of P-450E demonstrated here indicates a metabolic heterogeneity which could influence the responses of different cell types to subsequent or continued exposure to PAH or other hepatotoxins.