ToxSci Advance Access originally published online on April 7, 2004
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Toxicological Sciences 80, 26-33 (2004)
Toxicological Sciences vol. 80 no. 1 © Society of Toxicology 2004; all rights reserved.
Glutathione S-Transferase Expression in Pollution-Associated Hepatic Lesions of Brown Bullheads (Ameiurus nebulosus) from the Cuyahoga River, Cleveland, Ohio
Department of Physiological Sciences, Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida 32611-0885
Received January 7, 2004; accepted March 15, 2004
In rodents, overexpression of glutathione S-transferase pi is a characteristic feature of foci of cellular alteration (FCA) and neoplastic liver lesions induced by genotoxic chemicals. Alterations of glutathione S-transferase (GST) expression in hepatic lesions have also been reported in fish exposed to environmental carcinogens, and cellular GST expression may be an important determinant of growth and progression of chemical-associated liver tumors in certain fish species. In the present study, GST expression was examined in hepatic lesions of brown bullheads (n = 44) from the Cuyahoga River, a highly industrialized site located in Cleveland, Ohio. GST proteins were detected by immunohistochemistry and polyclonal antibodies that recognize either two major bullhead GST proteins or a pi-like GST isoform. Hepatic lesions were present in 70% of the fish and included biliary hyperplasia and biliary fibrosis; eosinophilic, basophilic, clear cell, and vacuolated FCA; and biliary neoplasms. Eosinophilic FCA and biliary tumors were the most prevalent preneoplastic and neoplastic lesions. GST expression in hyperplastic biliary tissue, FCA and tumors did not markedly differ from that of surrounding normal hepatocytes or biliary epithelium. Some hepatocytes within eosinophilic FCA had decreased GST expression. A complete absence of GST immunoreactive protein was not observed in any lesion, and there were no marked differences when comparing GST pi to overall GST expression. Our results indicate that GST expression in hepatic lesions of brown bullhead exposed to environmental carcinogens does not significantly differ from that in surrounding normal cells and is therefore not a useful predictor of environmental carcinogenesis in this species. Furthermore, the regulation and expression of GST pi in bullhead hepatocarcinogenesis appears to differ markedly from that during hepatocarcinogenesis in rats and some other fish species.
Key Words: glutathione S-transferase; altered foci; immunohistochemistry; cholangiocellular carcinoma; brown bullhead; liver; neoplasia.