The Significance of Preneoplastic Liver Lesions in Experimental Animals

Williams, Gary M.

doi:10.1016/b978-0-12-039231-5.50007-3

Cited by 16 publications

(8 citation statements)

References 96 publications

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“…GST-P is a typical marker of enzyme-altered foci in liver carcinogenesis (26)(27)(28)(29)(30). Liver cell foci have been reported to have some characteristic changes and recognized to be the preneoplastic lesion and the precursor of liver neoplasms in the hepatocarcinogenesis (20)(21)(22)(23)(24)(25). Many investigators (20)(21)(22)(23)(24)(25) have studied hepatocarcinogenesis analyzing the enzyme altered foci, using markers such as GST-P, y-glutamyltranspeptidase (GGT), adenosine triphosphatase, glucose-6-phosphatase, and others.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study suggested that the AOM also induces hepatocellular lesions including neoplasms and foci, which have been reported to be preneoplastic lesions of the liver (19). The preneoplastic lesions of liver have been shown to have altered phenotypic expression (20)(21)(22)(23)(24)(25). There are several studies to suggest that glutathione S-transferase placental form (GST-P) is one of the positive marker enzymes for hepatocellular foci induced by liver carcinogens and AOM (26)(27)(28)(29)(30)(31)(32).…”

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confidence: 99%

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Effect of fish oil on the development of AOM‐induced glutathione S‐transferase placental form positive hepatocellular foci in male F344 Rats

Sugie

Okamoto

Tanaka

et al. 1995

Nutrition and Cancer

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Omega-3 fatty acids, which are contained in fish oils and certain vegetable oils in contrast to corn oil or safflower oil rich in omega-6 fatty acids (linoteic acid), have been reported to reduce the carcinogenesis in several organs. In this study, the modifying effect of menhaden fish oil was investigated on the occurrence of azoxymethane (AOM)-induced glutathione S-transferase placental form (GST-P) positive hepatocellular foci, recognized preneoplastic lesions in the liver, in male F344 rats. Starting at five weeks of age, groups of animals were fed ad libitum a semipurified diet containing 5% corn oil (low fat). At seven weeks of age, all animals except the vehicle-treated groups were injected subcutaneously with AOM (15 mg/kg body wt, 1x/wk for 2 wks). Four days after the second injection, groups of animals were fed the diets containing 4% menhaden oil + 1% corn oil (low fish oil diet), 22.5% menhaden oil + 1% corn oil (high fish oil diet), and 5% corn oil. Thirty-four weeks after AOM injections, all animals were necropsied. Livers were sectioned and performed immunohistochemical staining of GST-P for quantitative analysis of enzyme altered foci of the liver. The results demonstrate that the density and the unit area of AOM-induced enzyme altered foci in the liver were significantly lower in the high fish oil group (0.60 +/- 0.08/cm2, 3.0 +/- 0.4 x 10(-4)) than in the 5% corn oil group (2.71 +/- 0.33/cm2, 16.6 +/- 2.6 x 10(-4)) and the low fish oil group (1.66 +/- 0.33/cm2, 11.1 +/- 1.9 x 10(-4)).(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of fish oil on the development of AOM‐induced glutathione S‐transferase placental form positive hepatocellular foci in male F344 Rats

Sugie

Okamoto

Tanaka

et al. 1995

Nutrition and Cancer

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“…Altered hepatocellular foci (AHF) are considered to be part of the spectrum of neoplastic change (2,6,18,21,24) occurring spontaneously or induced by xenobiotics in liver. Although -not all AHF progress to neoplasia, they are considered to have the potential to do so and dose-related increases in AHF are regarded as added evidence in interpretation of carcinogenicity of certain compounds (13).…”

Section: Introduction _mentioning

confidence: 99%

Stereological Evaluation of Altered Hepatocellular Foci in Control Wistar Rats

Walsh¹,

Razmpour²

1992

Toxicol Pathol

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“…The in vitro evolution of the hepatocytes transfected in vitro or in vivo followed a similar pattern of cell hyperplasia which ended in the formarion of domes of multilayered cells and then of cell spheroids and nodules. Thus, transformarion of liver parenchymal cells by the Ha-ras EJ plasmid offers a peculiarly efficient tool to study not only cell differenciation processes but also tissue lesions due to hyperplasic module formation (Farber, 1956 and1984;Williams, 1987) and macromolecular alternations in order to localize the target site of the ras oncogene in the recipient DNA and of the related protein in the plasma membrane. More trivially such proliferative hepatocytes may imply much development in the in vitro study of drug metabolism.…”

Section: Ha-ras Gj Transformationmentioning

confidence: 99%

Maintenance of liver function in long term culture of hepatocytes following In Vitro or In Vivo Ha-ras EJ transfection

et al. 1991

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Collagenase isolated rat hepatocytes were transfected with liposome encapsulated pEJ (LE-pEJ), a plasmid carrying the human cellular activated Ha-rasEJ oncogene. A proliferative cell line was cloned from these cells transfected in vitro. It secreted per day 0.87 micrograms albumin and 0.32 microgram transferrin per 10(6) cells, and 11.06 nmol free and conjugated bile acids (BA) per mg protein. Also, it metabolized 2-acetylaminofluorene (2-AAF) into N- and ring-hydroxylated metabolites and 2-aminofluorene at rates of 1.50, 9.73, and 1.98 nmol/mg cell protein/24 hr, respectively. Rats were i.v. injected with both LE-pEJ and LE-p17hGHneo carrying the hGH cDNA gene, and secreted hGH in the plasma which induced the synthesis of anti-hGH antibodies. A cell line was cloned from cultures of primary hepatocytes isolated from the liver of transfected rats. After 2 to 3 months in culture, this cell line secreted per day 18.9 micrograms albumin and 11.0 micrograms transferrin per 10(6) cells, 38.75 nmol total BA per mg cell protein, and up to 31 ng hGH per 10(6) cells without cloning hGH recombinant cells. A 24 hr control culture of primary hepatocytes isolated from non transfected rats secreted 25.5 micrograms albumin and 11.7 micrograms transferrin per 10(6) cells, and produced 21.64 nmol total BA and 2.13 nmol N-OH-2-AAF per mg cell protein. Hence, Ha-rasEJ transfection of either hepatocytes in vitro or liver cells in vivo, initiated cell cycles leading to presumptive proliferating hepatocytes which express liver function.

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The Significance of Preneoplastic Liver Lesions in Experimental Animals

Cited by 16 publications

References 96 publications

Effect of fish oil on the development of AOM‐induced glutathione S‐transferase placental form positive hepatocellular foci in male F344 Rats

Effect of fish oil on the development of AOM‐induced glutathione S‐transferase placental form positive hepatocellular foci in male F344 Rats

Stereological Evaluation of Altered Hepatocellular Foci in Control Wistar Rats

Maintenance of liver function in long term culture of hepatocytes following In Vitro or In Vivo Ha-ras EJ transfection

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