1,721,058 research outputs found
Lead and liver cell proliferation. Effect of repeated administrations.
No full textThe effect of repeated treatments with lead on hepatic cell proliferation was investigated in male Wistar rats. The animals were given intravenous injections of lead nitrate once every 10 days for 30 and 80 days. At the end of the experimental regimen, enlargement of the liver, accompanied by an increase in hepatic DNA content, was observed. A significant enhancement in the incorporation of labeled thymidine into hepatic DNA was found in lead-treated rats at the time intervals mentioned above, when compared with controls. An increase in the number of liver cells involved in mitosis was also observed in lead-treated animals. Analysis of serum glutamic-pyruvic transaminase and histologic observations did not show any sign of cell death at the time points examined. These results indicate that liver cells exposed to repeated treatments with lead undergo proliferation. However, a progressive reduction in the capacity of hepatic cells to divide was found in rats given repeated administrations of the metal, when compared with the extent of cell proliferation induced by a single dose of lead nitrate
Metabolic properties of isolated rat liver cell preparations enriched in epithelial cells other than hepatocytes.
No full textCell proliferation, cell death and hepatocarcinogenesis
No full textThe carcinogenic process in the liver is a multistep process, characterised by an altered ratio between cell proliferation and cell death. In the last few years, we have undertaken studies aimed at determining the possible differences exhibited by two different types of cell proliferation, namely compensatory regeneration and direct hyperplasia at a molecular and cellular level. These two types of proliferative stimuli appear to play different roles in liver carcinogenesis. The scope of this article is to summarise the present knowledge about the differences in the expression of genes involved in the entry of liver cells into cell cycle, between liver regeneration following cell loss and/or cell death and direct hyperplasia induced by primary mitogens
Failure of mitogen-induced cell proliferation to achieve initiation of rat liver carcinogenesis.
No full textExperiments were designed to determine whether mitogen-induced cell proliferation is as effective as regenerative cell proliferation in achieving initiation of liver carcinogenesis. To test this hypothesis male Wistar rats were injected with a single dose of diethylnitrosamine (DENA) or N-methyl-N-nitrosourea (MNU) during the peak of DNA synthesis following the administration of the liver mitogen, lead nitrate, after partial hepatectomy (PH) or a necrogenic dose of CCl4. The initiated hepatocytes were monitored as gamma-glutamyltransferase (GGT)-positive foci using a 2-week selection regimen consisting of 0.03% 2-acetylaminofluorene (2-AAF) coupled with a necrogenic dose of CCl4. The results indicate that unlike compensatory cell proliferation such as that induced by PH or CCl4, mitogen-induced cell proliferation did not result in any initiated hepatocytes despite the fact that in both types of models the extent of liver cell proliferation at the time of the administration of the carcinogen is similar
Mitogenesis by ligands of nuclear receptors: an attractive model for the study of the molecular mechanisms implicated in liver growth
No full text
Dietary orotic acid, a new selective growth stimulus for carcinogen altered hepatocytes in rat
No full textIt was observed that orotic acid (OA), a precursor for pyrimidine nucleotide biosynthesis, when supplied exogenously at 1% level in the diet selectively stimulated the growth of hepatocytes modified by 1,2-dimethylhydrazine (1,2-DMH) to form gamma-glutamyltransferase (gamma-GT) (EC 2.3.2.2) positive islands. Increasing the duration of OA diet from 5 to 10 weeks resulted in an increase in the number of foci from 6 to 14/cm2. Rats that received the carcinogen and basal diet, however, developed only 1-2 foci/cm2. This unique effect of OA can be further accentuated by supplying a liver cell proliferative stimulus, such as a single necrogenic dose of CCl4
Susceptibility of dimethylnitrosamine induced O6-methylguanine containing regions in in vivo replicated, hybrid rat liver DNA towards S1 nuclease
No full textAlpha-lipoic acid promotes the growth of rat hepatic preneoplastic lesions in the choline deficient model
No full textalpha-lipoic acid (alpha-LA) is an antioxidant used in a number of conditions related to liver diseases. Herein, we investigated the effect of alpha-LA on the development of rat pre-neoplastic lesions generated by a model of hepatocarcinogenesis, which has similarities in its histopathological sequence to human hepatocellular carcinoma development with cirrhosis. Initiation of hepatocytes was achieved by treatment with a single dose of diethylnitrosamine and promotion by feeding a choline-methionine-deficient diet (CMD), with or without alpha-LA. Pre-neoplastic lesions were identified by their positivity to the placental form of glutathione S-transferase (GSTP) or to gamma glutamyl transpeptidase. alpha-LA given to rats fed a CMD for 6 weeks dramatically increased the number of GSTP-positive foci as compared with rats fed a CMD alone (96/cm(2) versus 7/cm(2)), the mean foci area (0.033 versus 0.008 mm(2)) and the percentage of GSTP-positive liver tissue (3.01 versus 0.07%). Essentially similar results were obtained after 10 weeks of treatment. Co-treatment with CMD + alpha-LA also resulted in the enhancement of fat accumulation, lipid peroxidation and hepatocyte death; increased expression of tumor necrosis factor-alpha, cytochrome 2E1 and cyclooxygenase-2, enhanced activation of c-jun N-terminal kinase and signal transducer activator of transcription 3, and chronic hepatocyte proliferation was also observed. No such effects were observed when alpha-LA was added to a choline-supplemented diet. In conclusion, administration of alpha-LA in conditions associated with hepatic damage aggravates liver injury and stimulates the development of pre-neoplastic lesions; the results also suggest caution in its use in the presence of chronic liver injur
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