IMMUNOHISTOCHEMICAL LOCALIZATION OF CYTOCHROME P4501A IN MULTIPLE TYPES OF CONTAMINANT-ASSOCIATED HEPATIC-LESIONS IN ENGLISH SOLE (PLEURONECTES VETULUS)

Variations in the expression of cytochrome P450 (CYP) isozymes in cell s may affect the response of and consequent toxic effects in those cel ls during xenobiotic exposure. The expression of cytochrome P4501A (CY P1A), a major inducible CYP in teleosts, was examined immunohistochemi cally in multiple toxicopathic hepatic lesion types, including neoplas ms and several types of preneoplastic foci of cellular alteration (FCA ), in English sole (Pleuronectes vetulus) captured from the Duwamish W aterway, a highly contaminated estuary of Puget Sound, WA. Formalin or Bouin's-fixed, paraffin-embedded tissue sections were stained with po lyclonal rabbit anticod CYP1A IgG by the avidin-biotin peroxidase comp lex method; this antibody binds to both Atlantic cod (Gadus morhua) an d English sole CYP1A in Western blotting and ELISA, and immunohistoche mically-localizes CYP1A in hepatic and other tissues of cod exposed to beta-naphthoflavone. CYP1A-associated staining intensity was lower in hepatocellular and cholangiocellular neoplasms, areas of biliary hype rplasia, and normal intrahepatic exocrine pancreas and bile ducts, as compared to histologically normal hepatocellular parenchyma. FCA of ba sophilic, eosinophilic and clear cell types showed variable staining i ntensities in comparison to background parenchymal staining, but gener ally showed reduced CYP1A-associated staining. Staining intensity for a single hemangiopericytic sarcoma showed highly reduced staining for CYP1A. These results, in fish naturally exposed to environmental toxic ants, suggest a parallel response between teleosts and mammals with re spect to CYP1A expression and resistance to cytotoxicity in cells comp osing several types of hepatic neoplasms and foci of cellular alterati on.