Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated c-Ha-ras DNA sequences were introduced by transfection into a low passage simian virus 40 (SV40)-immortalized rat hepatocyte cell line, CWSV1, and stable ras transfectant cell lines were established to determine the effect of the addition of the activated c-Ha-ras oncogene on growth properties and differentiation. Control transfectant cell lines were generated by transfection with neo alone. CWSV1 cells at low passage and the control transfectants were not tumorigenic. The ras transfectants demonstrated anchorage-independent growth and were highly tumorigenic in syngeneic hosts. CWSV1 cells produce liver-like levels of albumin and express other liver-specific genes. The ras transfectants expressed RNA for albumin, transferrin, and the transcription factor HNF-1 at similar levels to the parental CWSV1 cells, indicating that the alterations in growth properties and tumorigenic potential of these cells did not decrease the ability of the cells to express several genes that are associated with hepatocyte differentiation. The addition of the ras oncogene did not induce the expression of alpha-fetoprotein and had no specific effect on expression of glutathione S-transferase-P. The tumors produced by the ras transfectants were not well differentiated; however, the cells in the tumors and tumor cell lines derived from the tumors continued to produce albumin and did not produce alpha-fetoprotein. We conclude that the addition of the activated c-Ha-ras oncogene to immortalized CWSV1 cells transformed these cells as measured by morphology, growth properties, and tumorigenicity without reducing their ability to express albumin and other significant liver-specific genes.
 ...
PMID:Introduction of the ras oncogene transforms a simian virus 40-immortalized hepatocyte cell line without loss of expression of albumin and other liver-specific genes. 137 Oct 91

In order to investigate the early cellular changes in liver associated with furan cholangiocarcinogenesis, young adult male Fischer 344 rats were administered furan by gavage once a day, 5 days a wk for 2 to 3 wk at doses ranging from 15 to 60 mg/kg of body weight per day. The most conspicuous feature observed in the liver of animals receiving the higher doses of furan was a rapidly developed cholangiofibrosis characterized by the presence of bile ductular hyperplasia, intestinal metaplasia, and fibrosis. Moreover, this lesion was found to be almost exclusively localized to the caudate liver lobe, which by morphometric analysis was further determined to be largely replaced by cholangiofibrotic tissue. Both the hyperplastic bile ductular epithelial cells and the intestinal-like epithelial cells in these areas selectively exhibited a strongly positive immunohistochemical staining for cytokeratin 19 and were supported by well-developed basement membranes enriched in both laminin and type IV collagen. However, in contrast to the hyperplastic bile ductules, electron microscopy of the metaplastic intestinal glands revealed them to be composed mostly of columnar epithelial cells with well-developed striated borders, less numerous mucin-secreting goblet cells, and occasional neuroendocrine-like cells, thus closely resembling in their cellular composition that of intestinal mucosa. These metaplastic glands also showed a more heterogeneous pattern of staining for both gamma-glutamyl transpeptidase and the placental form of glutathione S-transferase than did the hyperplastic bile ductules. At the 60-mg/kg/day furan dose, cholangiolar-like structures composed of biliary epithelial cells and ductular hepatocytic cells at different stages of morphological differentiation were also observed. Phenotypically, the biliary epithelial and "ductular hepatocytes" of these cholangioles shared a common basement membrane containing laminin and type IV collagen, as well as a luminal plasma membrane gamma-glutamyl transpeptidase. On the other hand, only the biliary epithelial cells of the newly appearing mixed cell cholangioles stained positive for cytokeratin 19. Interestingly, unlike hepatocarcinogen-induced oval cells, alpha-fetoprotein expression was not detected in any of the cell types comprising the furan-induced cholangiofibrotic tissue. These results support a novel in vivo model for investigating cell lineages in the development in liver of intestinal metaplasia, "ductular hepatocytes," and cholangiofibrosis in relation to intrahepatic cholangiocarcinogenesis.
 ...
PMID:Phenotypic characterization of metaplastic intestinal glands and ductular hepatocytes in cholangiofibrotic lesions rapidly induced in the caudate liver lobe of rats treated with furan. 165 60

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 pseudoductal formations 32 or 56 h after partial hepatectomy at the periphery of the periductal space in both initiated and uninitiated animals. A combination of in situ and immunohistochemistry revealed that the OV-6-positive cells were AFP positive, whereas desmin-positive cells were AFP negative. Glutathione S-transferase P (GST-P) transcripts could be found mainly in OV-6-positive oval cells. Bile duct cells were positive for GST-P and negative for transforming growth factor beta 1, whereas cells in the periductal space were positive for both of these transcripts. The GST-P-positive early preneoplastic lesions showed a similar distribution pattern as that of oval cells; the preexisting hepatocytes became trapped between small basophilic hepatocytes that showed either irregular or pseudoalveolar arrangement. This raises the question as to whether cells which are stem cell-like are among the target cells in the Solt-Farber model of hepatocarcinogenesis. Proliferation of transforming growth factor beta 1-producing, desmin-positive cells (Ito cells) and multipotent oval cells in a close proximity to each other indicates an intricate relationship between Ito cells and oval cells in liver that warrants further investigation.
 ...
PMID:Cellular and molecular changes in the early stages of chemical hepatocarcinogenesis in the rat. 169 60

The incidence and phenotype of preneoplastic and neoplastic liver lesions appearing in LEC rats after recovery from severe hereditary hepatitis were studied in comparison with the liver lesions appearing in chemical liver carcinogenesis. The livers of 168 rats (90 male, 78 female) were stained for seven histochemical markers at different time periods from the 20th week to the 122nd week of life. Glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and non-specific esterase (ES) were used as negative markers. Gamma-glutamyltransferase (GGT), glutathione S-transferase placental form (GSTP), esterase isozyme L-1 (L1) and alpha-fetoprotein (AFP) were used as positive markers. The study on the incidence of liver lesions in the LEC rats revealed sequential development of liver foci, nodules and hepatocellular carcinomas (HCCs) similar to those seen in chemically induced liver carcinogenesis. These lesions appeared earlier and more frequently in male LEC rats than in female ones, suggesting the importance of hormonal environment in spontaneous HCC development. The histochemical analysis of spontaneous liver lesions in LEC rats showed that GSTP was the most reliable positive marker as previously reported in chemical liver carcinogenesis. There was no essential difference in the expression of the markers in spontaneous and chemically induced liver lesions except for L1, which is considered to be related to xenobiotic metabolism. The results of this study suggest that both spontaneous and chemically induced liver cancer may develop by passing through phenotypically similar preneoplastic processes. In addition, the LEC rat uniquely showed chronic liver damage (hepatocyte death and regeneration) at the promotion stage of carcinogenesis. Such a natural history of HCC development in LEC rats is similar to that of human HCC which is frequently associated with chronic liver damage. Thus, the LEC rat provides a useful model for studying the process and underlying mechanisms of human liver cancer development.
 ...
PMID:Phenotype of preneoplastic and neoplastic liver lesions during spontaneous liver carcinogenesis of LEC rats. 169 69

The phenotypic response of rat liver to a carcinogenic protocol involving initiation/selection and promotion with and without phenobarbital (PB) feeding was studied in pubertal and adult male rats. Considering the early presence of preneoplastic nodular areas, it appeared that pubertal rats, initiated at 6-7 weeks, presented a higher susceptibility to the protocol than adult rats initiated at 9-10 weeks. Altered liver phenotype was characterized by: (1) gamma-glutamyl-transpeptidase (GGT) and glutathione S-transferase (GST) activities; (2) the expression of two forms of cytochrome P-450; de novo PB-inducible P-450 II B 1,2 and P-450 II C 7 normally expressed in 45-day-old rats and PB-inducible, and (3) the expression of albumin and alpha-fetoprotein cDNAs. In the absence of PB, the susceptibility of pubertal rat liver to hepatocarcinogenesis was related to a special metabolic phenotype enriched in GGT and GST activities by comparison with the quasi-normal expression of both P-450s. Adult rat liver presented a less altered pattern closer to that of noninitiated rat liver. During PB promotion, the loss of PB inducibility of P-450 II C 7 in pubertal rat liver suggested that the hormonal status of the animals could interact with initiation to modulate specific gene expression. The late phase of PB promotion revealed the loss of highly differentiated functions (P-450s, albumin), whereas enzymatic markers associated with preneoplastic foci showed a persistent high expression.
 ...
PMID:Effect of rat developmental stage at initiation on the expression of biochemical markers during liver tumor promotion. 170 Aug 61

The appearance of differentiated hepatocytes in the adult rat pancreas as well as pancreatic-type tissue in the adult rat liver can be experimentally induced (Reddy et al.: J. Cell Biol., 98:2082-2090, 1984; Rao et al., J. Histochem. Cytochem., 34:197-201, 1986). These observations suggest a lineage relationship between cell compartments present in rat liver and pancreas. The present data demonstrate that epithelial cell lines with almost identical phenotypes can be established from adult rat liver and pancreas. The established cell lines showed similar morphologies as established by light- and electron-microscopic studies. The cell lines showed a unique expression pattern of intermediate filament proteins. Vimentin, actin, and beta-tubulin were present in all cell lines. In addition, simple epithelial type II cytokeratins 7 and 8 were found to be coexpressed with the type I cytokeratin 14 in several of the cell lines. Neither the type I cytokeratins 18 and 19, which are the normal partners for cytokeratins 8 and 7 in filament formation, nor the type II cytokeratin 5 could be detected despite the fact that filaments were formed by both cytokeratins 8 and 14. This suggests that cytokeratin 14 acts as an indiscriminate type I cytokeratin in filament formation in the established cell lines. The cell lines expressed the same sets of LDH and aldolase isoenzymes and identical sets of glutathione transferase subunits. In addition, the epithelial cell lines from liver and pancreas were equally sensitive to the growth-inhibitory effects of TGF-beta 1. No expression of tissue- or cell-specific proteins such as alpha-fetoprotein, albumin, amylase, elastase, or gamma-glutamyl transpeptidase were detected. The almost identical phenotypes of the hepatic and pancreatic cell lines suggest that they may be derived from a common primitive epithelial cell type present in both rat liver and pancreas. In contrast to parenchymal cells, these cells have an extended capacity for proliferation in vitro and may represent a progeny from a "precursor" or "stem" cell compartment in vivo.
 ...
PMID:Evidence for a common cell of origin for primitive epithelial cells isolated from rat liver and pancreas. 171 Feb 29

1. Antisera to native or unfolded glutathione S-transferase from human liver recognize either antigen but do not recognize native or unfolded glutathione S-transferase from human placenta. 2. Antisera to native or unfolded glutathione S-transferase from placenta recognize either antigen but do not recognize native or unfolded glutathione S-transferase from liver. 3. Antisera to unfolded human serum albumin crossreacts with unfolded alpha-fetoprotein but does not recognize unfolded glutathione S-transferase.
 ...
PMID:Immunochemical comparisons of proteins that bind heme and bilirubin: human serum albumin, alpha-fetoprotein and glutathione S-transferases from liver, placenta and erythrocyte. 244 26

Many structurally unrelated nonmutagenic peroxisome proliferators induce altered areas, neoplastic nodules, and hepatocellular carcinomas in rats. Unlike the lesions induced by genotoxic hepatocarcinogens, these lesions do not stain positively for the phenotypic markers gamma-glutamyl transpeptidase (GGT) and glutathione-S-transferase P (GST-P). To ascertain whether the absence of immunocytochemically detectable GST-P and GGT proteins in peroxisome proliferator-induced neoplastic lesions is due to the absence of specific mRNAs, we analyzed the total RNA isolated from hepatocellular carcinomas induced by three different peroxisome proliferators (ciprofibrate, Wy-14643, and BR-931) and the genotoxic carcinogens, 2-acetylaminofluorene and aflatoxin B1 (AFB), for the presence of GST-P, GGT, and alpha-fetoprotein (AFP) mRNAs. Northern and dot blot analysis of total RNA isolated from liver tumors induced by three different peroxisome proliferators revealed no detectable GST-P, GGT, and AFP mRNAs. GST-P mRNA was also not detected in a transplantable hepatocellular carcinoma established from a liver tumor induced by ciprofibrate. In contrast, GST-P mRNA levels were high in primary liver tumors induced by both 2-acetylaminofluorene and AFB and the two transplantable hepatocellular carcinomas established from such tumors. By immunoblot method, GST-P protein was found to be abundant in both primary and transplantable liver tumors induced by genotoxic carcinogens but not in those derived from peroxisome proliferator treatment. The GGT and AFP mRNAs were also not found in all 18 liver tumors induced by peroxisome proliferators that were analyzed and also in the ciprofibrate-derived transplantable liver tumor. The expression of GGT and AFP genes in liver tumors induced by 2-acetylaminofluorene and AFB was variable. These studies with peroxisome proliferators show that the GST-P and GGT gene derepression is not essential for the hepatocarcinogenesis or successful tumor transplantation. Further characterization of the molecular basis for the differential expression, particularly of the GST-P gene in liver tumors, may help identification of the critical event(s) in hepatocarcinogenesis by genotoxic carcinogens and nongenotoxic peroxisome proliferators.
 ...
PMID:Lack of expression of glutathione-S-transferase P, gamma-glutamyl transpeptidase, and alpha-fetoprotein messenger RNAs in liver tumors induced by peroxisome proliferators. 245 33

A primary endodermal sinus tumour of the liver which developed in a 27-year-old woman is reported. The dimensions of the tumour were 11 x 11 x 9.5 cm. Most parts were friable, haemorrhagic, and necrotic. No metastasis was found, but one part of the tumour was invading the diaphragm directly. Histologically, the tumour had mainly a reticular pattern, and partly a solid pattern, and was characterized by the presence of Schiller-Duval bodies and intra- and extracellular hyaline globules. A small part of the tumour showed a polyvesicular vitelline pattern and glandular structures with enteric differentiation. Serum alpha-fetoprotein was very high (28,500 ng/ml), but carcinoembryonic antigen was within the normal range. Immunohistochemically, most of the tumour cells contained alpha-fetoprotein and alpha-1-antitrypsin. Carcinoembryonic antigen and glutathione S-transferase, which was recently proved to be a useful marker for colonic carcinoma, were detected only in the glandular part Four previously reported cases of primary endodermal sinus tumour of the liver are reviewed.
 ...
PMID:Endodermal sinus (yolk sac) tumour of the liver. A case report and review of the literature. 328 36

The oval cells of the liver have been identified as target cells of chemical carcinogens during rat hepatocarcinogenesis and are believed to act as liver stem cells. In this study mice (strains C3H/EJ (C3H), C57/BL6J (C57) and hybrid B6C3F1 (F1)) were sacrificed at 1, 3 and 7 days after administration of a single dose of the carcinogen diethylnitrosamine (DEN), and histopathological studies of oval cells were evaluated using Haematoxylin and Eosin (H&E), Picro-Mallory (P-M), alpha-fetoprotein (A-FP) and glutathione S-transferase placental form (GST-pi) staining techniques and electron microscopy (EM). Increased oval cell proliferation was observed as soon as one day following exposure of the mice to DEN, in a manner consistent with C3H and C57 mice exhibiting high and low susceptibility to DEN respectively, with hybrid F1 mice being intermediate in DEN sensitivity. This analysis indicates that, in mice, oval cells are target cells at very early stages of liver carcinogenesis and supports the notion that oval cells are potential liver stem cells.
 ...
PMID:Short-term diethylnitrosamine-induced oval cell responses in three strains of mice. 752 17


1 2 3 Next >>