Isozyme profiles of oval cells, parenchymal cells, and biliary cells isolated by centrifugal elutriation from normal and preneoplastic livers (original) (raw)
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Cellular and molecular changes in the early stages of chemical hepatocarcinogenesis in the rat
Cancer research, 1990
The early cellular and molecular changes in the Solt-Farber model of hepatocarcinogenesis with and without initiation was studied by using histochemical, immunohistochemical, and in situ hybridization techniques. Increased cellularity was observed in the periductal space in both models 32 to 56 h after partial hepatectomy. These periductal cells and Ito cells were the only cells that became labeled with tritiated thymidine in the uninitiated liver model. Forty-five to 60% of the labeled periductal cells were positive for gamma-glutamyltranspeptidase. From the periductal area the cells that were positive for antibody raised against oval cells (OV-6) infiltrated into liver parenchyma and were followed by desmin-positive Ito cells. The number of Ito cells in the uninitiated model 6 days after partial hepatectomy was 3.5 times higher in the area occupied by oval cells than elsewhere in the liver. The first alpha-fetoprotein (AFP)-positive cells appeared either as individual cells or as ...
Carcinogenesis, 1998
Rats received a choline-deficient diet containing 0.1% (w/ w) DL-ethionine (CDE) for 4, 10, 14 or 22 weeks. A separate group was treated for 4 weeks with CDE and then received a normal diet for 4 weeks. The L and M 2 isoenzymes of pyruvate kinase were immunocytochemically demonstrated in liver sections. L-PK expression was strongly reduced in the hepatocytes after 4 weeks of treatment and remained low until the end of the study. Withdrawal of CDE after 4 weeks followed by 4 weeks normal diet resulted in a nearly full recovery of L-PK expression as compared to untreated controls. At later stages (10-22 weeks of CDE-treatment) many pseudolobules, preneoplastic foci of altered hepatocytes (FAH) such as combined clear/acidophilic cell foci (CCF/ACF) and mixed/basophilic cell foci (MCF/BCF), and hepatocellular adenomas (HCA) were observed. Pseudolobules showed a slight reduction in L-PK-expression, and were negative for M 2-PK. In all clear cell components of CCF/ACF excessively storing glycogen, L-PK-expression was increased compared to both the surrounding parenchyma and hepatocytes of controls. In acidophilic cell components with less pronounced glycogen storage L-PK expression was similar to that of pseudolobules showing a slightly reduced content of this enzyme protein. M 2-PK was invariably negative in CCF/ACF. In most MCF glycogen-storing subpopulations expressed L-PK, whereas in all glycogen-poor basophilic populations L-PK protein was strongly reduced. M 2-PK was not expressed in most of these MCF. However, in rare MCF the reduction in L-PK expression was combined with a significant expression of M 2-PK. In HCA M 2-PK underwent a further increase, although to a variable degree, while L-PK remained strongly reduced. Our results show that an isoenzyme shift from L-PK to M 2-PK takes place at a late stage of the hepatocarcinogenic process, and that those MCF with a low L-PK expression and a reexpression of M 2-PK most probably represent the direct precursor lesions of hepatocellular neoplasms.
Endogenous liver carcinogenesis in the rat *
Pathology International, 1999
Carcinogenesis may be effected not only through exposure to exogenous stimuli but also by genetic and epigenetic influences derived from endogenous factors. In the latter case, the mechanisms are still largely obscure because of the limited availability of appropriate in vivo experimental models. However, continuous feeding of a diet deficient in choline and methionine is well known to cause hepatocellular carcinomas (HCC) in rats in the absence of any known exogenous carcinogens and can serve as a good research model. A semi-synthetic, choline-deficient, L-amino acid-defined (CDAA) diet, containing practically no choline and low methionine, induces HCC with a background of fatty liver and hepatocyte death, subsequent regeneration and fibrosis resulting in cirrhosis. Using the CDAA diet, we have revealed the participation of oxidative injury to DNA and other subcellular components and of alteration in intrahepatic signal transduction pathways in the mechanisms underlying this rat liver carcinogenesis model. In the present paper, the current understanding of endogenous rat liver carcinogenesis, due to dietary choline deficiency, is reviewed.
Contribution to the study of mouse liver chemical carcinogenesis
2016
Presidente: Doutor Victor Manuel Machado dos Reis Professor Associado com Agregação da Universidade de Trás-os-Montes e Alto Douro Vogais: Doutora Maria da Conceição da Cunha e Vasconcelos Peleteiro Professora Catedrática da Faculdade de Medicina Veterinária da Universidade de Lisboa Doutor Luís Felipe de La Cruz Palomino Professor Catedrático da Universidade de Santiago de Compostela Doutora Maria dos Anjos Clemente Pires Professora Associada com Agregação da Universidade de Trás-os-Montes e Alto Douro Doutora Paula Alexandra Martins de Oliveira Professora Associada com Agregação da Universidade de Trás-os-Montes e Alto Douro Doutor Francisco Alberto Pereira Peixoto Professor Associado com Agregação da Universidade de Trás-os-Montes e Alto Douro Doutora Rita Maria Pinho Ferreira Professora Auxiliar da Universidade de Aveiro
1987
Experiments were designed to determine whether liver cell prolifera tion induced by direct mitogens is as effective as compensatory cell proliferation consequent to previous cell loss, in supporting the growth of enzyme-altered islands in the liver induced by chemical carcinogens. Male VVisui r rats were given injections of a single nonnecrogenic dose of .\-nifthyl-.'V-nitrosoiirca or benzo(a)pyrene during the S phase following the administration of four different liver mitogens, namely, lead nitrate, ethylene dibromide, nafenopin, and cyproterone acetate, or during com pensatory cell proliferation following partial hepatectomy or a necrogenic dose of CCV The carcinogen-altered hepatocytes were monitored as yglutamyltransferase-or placenta! glutathione S-transferase-positive foci using a 2-wk promoting regimen consisting of 0.03% 2-acetylaminofluorene coupled with a necrogenic dose of CCI*. The results indicate that, unlike compensatory cell proliferation induced by partial hepatectomy or CCI«the mitogen-induced cell proliferation did not result in a significant number of enzyme-altered islands, despite the fact that the extent of cell proliferation at the time of carcinogen administration, as monitored by the examination of labeled cells, is similar with both types of proliferative stimuli.
Journal of Cancer Research and Clinical Oncology, 1982
The livers of rats treated for 12 weeks with N-nitrosomorpholine (80 mg/1 drinking water) were investigated on the day of carcinogen withdrawal (12 + 0 weeks) and 8 weeks after cessation of treatment (12 + 8 weeks). The glycogen content in relation to the DNA and protein content of the liver and the activities of glycogen synthetase, glycogen phosphorylase, glucose-6-phosphatase, and glucose-6-phosphate dehydrogenase were determined in the liver homogenates. The glycogen content of the livers was slightly elevated at both times investigated. Phosphorylase and synthetase activities showed no clear alterations in livers of treated animals as compared with controls. Glucose-6phosphatase activity was significantly reduced at 12 + 0 weeks and returned to normal values at 12 + 8 weeks. The activity of glucose,6-phosphate dehydrogenase was unchanged at 12 + 0 weeks, but exhibited a significant increase at 12 § 8 weeks. Polyacrylamide gel electrophoresis with staining of the gels by an assay specific for the glucose-6-phosphate-dehydrogenase-catalysed reaction revealed the same pattern of active bands in treated and untreated animals but with higher acitivities in two bands originating from extracts of nitrosomorpholine-treated livers.
European journal of cancer & clinical oncology, 1982
The hepatocarcinogen 3'-methyl-4-dimethyl-aminoazobenzene (MDAB) suppresses the accumulation of tyrosine aminotransferase in cultured foetal hepatocytes. Experiments involving liver derived from foetuses of various ages reveals that a response is only obtained with rats older than 16-day gestation. It has been proposed that the lack of an effect in less mature hepatocytes is due to their inability to activate the carcinogen. Chemically synthesized analogues of MDAB which are considered likely to be activated forms of the procarcinogen are shown to be effective in the less mature cells. This supports the proposal that these cells may be unresponsive because they are unable to activate MDAB. Tests with other carcinogens reveal that the hepatocarcinogen dimethylbenzanthracene is also effective in 19-day gestation hepatocytes. However, the non-hepatocarcinogens azaserine and benz(a)pyrene are ineffective. Treatment with MDAB is shown not to alter the level of steroid receptor and re...