Histogenese und Cytogenese von Cholangiofibromen und Cholangiocarcinomen bei Nitrosomorpholin-vergifteten Ratten

Bannasch, Peter; Massner, B.

doi:10.1007/bf00506497

Cited by 58 publications

(17 citation statements)

References 21 publications

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“…The pre-dominant cell lineage observed during the development of hepatocellular carcinomas in the rat ranges from clear and acidophilic cell foci, which store glycogen in excess and may be acidophilic due to the proliferation of smooth endoplasmic reticulum, through mixed and basophilic (ribosome-rich) cell foci to hepatocellular adenomas and carcinomas [3]. The development of cholangiocellular neoplasms proceeds in four stages: proliferation of oval cells in response to the toxic effects of the chemicals on the liver parenchymal cells; appearance of cholangiofibroses, in which the bile duct epithelial cells store and secrete neutral and acidic mucopolysaccharides; appearance of cholangiofibromas, which grow expansively and produce collagen fibres and also mucous substances; appearance of cholangiocarcinomas, which grow invasively and show a gradual decrease of mucus production [4,5,19,30]. Oval cells are liver epithelial cells that proliferate during the early stages of hepatocarcinogenesis and severe liver injury induced by many chemicals [1].…”

Section: Introductionmentioning

confidence: 99%

Expression of pyruvate kinase M 2 in preneoplastic hepatic foci of N -nitrosomorpholine-treated rats

et al. 1999

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The expression of the pyruvate kinase (PK) isoenzymes L and M2 was analysed in the livers of rats treated with the hepatocarcinogenic agent N-nitrosomorpholine (NNM) in the drinking water. In control animals L-PK expression was restricted to liver parenchymal cells, whereas M2-PK was detected in bile duct epithelial, blood vessel wall, endothelial and Kupffer cells. In rats treated with NNM proliferating oval cells were consistently L-PK negative and M2-PK positive, while the ductal cells of cholangiofibroses were clearly L-PK positive and coexpressed M2-PK. However, no morphological differentiation of ductal cells into hepatocyte-like cells was observed. In the clear and acidophilic cell foci storing glycogen in excess strong staining for L-PK was observed. In glycogen-poor foci induced by NNM a shift from L-PK to M2-PK expression takes place.

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Section: Introductionmentioning

confidence: 99%

Expression of pyruvate kinase M 2 in preneoplastic hepatic foci of N -nitrosomorpholine-treated rats

et al. 1999

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“…However, there is increasing evidence to suggest that this may vary with the carcinogenic regimen used to generate such tumors [65], In azo dye carcino genesis in rats, oval cells are believed to be the precursors of cholangiofibrosis and of cholangiocarcinomas, and possibly of hepatocellular carcinomas and cholangiohepatomas [ 13,65,134,152]. Nonoyama et al [153] have also recently demonstrated a possible relationship be tween oval cells and the development of hepatoblasto mas in mice fed 2-acetylaminofluorene in an AIN-76A diet.…”

Section: Relationship To Hepatic Tumor Development In Vivomentioning

confidence: 99%

Isolation, Culture, and Transplantation of Intrahepatic Biliary Epithelial Cells and Oval Cells

et al. 1990

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Recent advances made in the isolation, culture, and transplantation of defined populations of intrahepatic biliary epithelial cells and oval cells have permitted direct analysis of the functions, growth properties, and differentiation potential of these respective cell types in their untransformed or transformed states. This review provides a current and comprehensive examination of the various approaches that have been taken to isolate and culture intrahepatic biliary epithelial cells from normal and cholestatic liver and oval cells from preneoplastic liver. Emphasis is placed on comparing the phenotypic features and growth properties of these various biliary cell types in vitro as well as on describing their transplantation into ectopic tissue sites. In addition, the oval cell is evaluated in terms of its potential role as a ‘facultative stem cell’ during hepatocarcinogenesis.

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“…The other three carcinomas had been induced by application for 66 weeks of both dimethylnitrosamine (0.3 mg/kg body weight) and Nnitrosopyrrolidine (0.5 mg/kg body weight) or of nitrosopyrrolidine (same dose) alone; tumors were found between weeks 12 and 14 after withdrawal of the drugs. Cholangiofibromas were induced as described (21) and taken from animals killed between weeks 60 and 64 after withdrawal of the drug. Five angiosarcomas were induced by application of both dimethylnitrosamine and nitrosopyrrolidine (doses as above), and animals were killed on day 87 after withdrawal.…”

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confidence: 99%

Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments.

Bannasch¹,

Zerban²,

Schmid³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

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Antibodies against constitutive proteins of different types of intermediate-sized filaments were used in immunofluorescence microscopy on frozen sections of normal rat liver and various rat liver tumors induced by treatment with nitrosamines. Antibodies to tonofilament prekeratin stained bile duct epithelia and hepatocytes of normal liver and hepatocellular carcinoma cells and ductal cells of cholangiofibromas. These cells were not significantly stained by antibodies to vimentin. By contrast, antibodies to vimentin stained mesenchymal cells of normal liver and cells of early and advanced angiosarcomas and of undifferentiated spindle cell sarcoma. These mesenchymal tumor cells were not stained with antibodies to prekeratin. (5,6,8,(11)(12)(13) has stimulated our interest in the possible maintenance of such molecular markers in tumors grown in the body.As a first example we have used the liver (in which different types of tumors, such as adenomas, hepatocellular carcinomas, cholangiofibromas, cholangiocarcinomas, angiosarcomas, and fibrosarcomas can occur) to determine whether epithelial and mesenchymal tumors could be distinguished by the use of antibodies to different filament proteins. The search for a molecular marker for identification of mesenchymal tumors of liver was especially desirable because mesenchymally derived liver tumors are important in human (14) and experimental animal (15) pathology. Reports of a high incidence of angiosarcomas in workers exposed to inorganic arsenic and gaseous vinyl chloride and in patients treated with Thorotrast or certain steroid hormones have increased the interest in this tumor (14, 16). The structure and morphogenesis of vascular liver tumors in humans and experimental animals appear to be largely identical (15,17). In both humans and animals, differential diagnosis of epithelial and mesenchymal liver tumors is sometimes difficult. A clear distinction, however, would be important not only for prognostic appraisals in human pathology but also for evaluation of animal experiments such as dose-response studies of carcinogenesis induced by chemical compounds (18, 19).In this study we show that immunofluorescence microscopy with antibodies to two molecular markers, prekeratin and vimentin, allows the character and origin of epithelial and mesenchymal cells to be distinguished in neoplastic liver cells and thus facilitates the differential diagnosis of liver tumors.MATERIALS AND METHODS Animals. Liver tumors were induced in male SpragueDawley rats (n-200 g body weight at the beginning of treatment) by oral treatment with nitrosamines (for methods, see ref. 20). Seven hepatocellular carcinomas, 3 cholangiofibromas, 10 angiosarcomas, and 1 undifferentiated spindle cell sarcoma were examined. Four of the hepatocellular carcinomas had developed in animals treated with 50 mg of N-nitrosomorpholine (in a total of 100 ml of their drinking water) for 3 weeks and killed between weeks 52 and 77 after withdrawal of the carcinogen. (Three of these carcinomas occurred in asso...

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Histogenese und Cytogenese von Cholangiofibromen und Cholangiocarcinomen bei Nitrosomorpholin-vergifteten Ratten

Cited by 58 publications

References 21 publications

Expression of pyruvate kinase M 2 in preneoplastic hepatic foci of N -nitrosomorpholine-treated rats

Expression of pyruvate kinase M 2 in preneoplastic hepatic foci of N -nitrosomorpholine-treated rats

Isolation, Culture, and Transplantation of Intrahepatic Biliary Epithelial Cells and Oval Cells

Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments.

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