Phenotypically altered hepatocyte populations in diethylnitrosamine-induced medaka liver carcinogenesis: Resistance, growth, and fate
A 5-week exposure of adult medaka (Oryzias latipes) to diethylnitrosamine (DEN. 50 ppm in aquarium water), followed by recovery, in clean water, results in hepatocellular carcinoma 12-16 weeks after initiation of exposure. Serial (weekly) morphometric evaluations estimated alterations within the liver. Enzyme histochemistry, marked putatively carcinogen-initiated hepatocytes in microscopic foci. Foci progressed, with time, to areas and nodules. The continued finding of hepatocyte necrosis in nonmarked populations and expansion of marked populations suggests resistance and growth of previously initiated cells. Cells marked by γ-glutamyl transpeptidase, quinone oxidoreductase (DT-diaphorase) and glucose-6-phosphate dehydrogenase were found in resultant neoplusms, suggesting linkage of focal phenotypes to eventual carcinomas. Tinctorial alterations and enzymic properties were compared in individual foci, areas, nodules and tumors. Biochemical verification of enhanced activity of γ-glutamyl transpeptidase and DT-diaphorase were obtained. © 1992.
Hinton, DE; Teh, SJ; Okihiro, MS; Cooke, JB; Parker, LM
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