Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high frequency of diploid and near-diploid clones were developed from cell lines derived from adult and newborn rat liver using micropipettes. There were some differences in morphology, biochemical properties and growth rate between clones. Cloned cells had low levels of tyrosine transaminase activity, glucose-6-phosphatase activity and albumin content. A diploid clone and pseudodiploid clone derived from adult rat liver cell line were positive for alpha-fetoprotein.
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PMID:Isolation and characterization of diploid clones from adult and newborn rat liver cell lines. 9 11

We studied the development of liver tumors in male transforming growth factor alpha (TGF-alpha) transgenic mice of the CD1 strain and examined the expression of the transgene by immunohistochemistry and in situ hybridization. Livers of 4-5-week-old transgenic mice contained areas of centribobular hypertrophy with low glucose-6-phosphatase activity. These areas progressively expanded, and hypertrophy and dysplasia became generalized in livers of mice at 10-12 months of age. The expression of the transgene, determined by either immunohistochemistry or in situ hybridization, was uneven in animals that were 10 weeks old or older. The positive hepatocytes formed patches with a predominant centrilobular distribution. We studied a total of 23 liver tumors (7 hepatocellular carcinomas and 16 adenomas) obtained from 11 mice at 13-15 months of age and from one 7-month-old animal which received zinc sulfate to induce the transgene. The carcinomas were well differentiated tumors, without glucose-6-phosphatase or gamma-glutamyltranspeptidase activity, that developed from the dysplastic parenchyma and occasionally within an adenoma. In all carcinomas and in 56% of the adenomas there was overexpression of the transgene in relationship to the surrounding tissue. The majority of the tumors that overexpressed TGF-alpha were alpha-fetoprotein positive, while alpha-fetoprotein staining was not detected in tumors (all adenomas) that did not show excessive transgene expression. We conclude that TGF-alpha functions as a promoter of liver carcinogenesis through its effect as an autocrine inducer of hepatocyte proliferation. Further, the data indicate that TGF-alpha overexpression may favor tumor progression.
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PMID:Development of liver tumors in transforming growth factor alpha transgenic mice. 132 2

Dichloroacetic acid (DCA) has recently been shown to increase significantly the incidence of hepatic adenomas (HAs) and hepatocarcinomas (HCs) in male B6C3F1 mice. Although little is known about the mechanism of DCA carcinogenesis, chronic ingestion of the compound in drinking water induces primarily hyperplastic nodules (HNs) prior to the appearance of HAs and HCs. Given the putative preneoplastic potential of the HNs, we undertook this study to determine the role of the HNs in the progression of DCA-induced hepatocarcinogenesis. This role was assessed by detecting the expression of five different tumor markers: p21 ras, p39 c-jun, phosphotyrosine, tumor-associated aldehyde dehydrogenase and alpha-fetoprotein, all known from previous studies to be expressed more often in neoplastic liver lesions than in normal liver. Tumor marker expression was detected by immunohistochemical methods using formalin-fixed, paraffin-embedded sections of normal B6C3F1 mouse liver, and DCA-induced HNs, HAs and HCs. The results demonstrated that, except for the c-jun marker, HNs expressed the markers significantly less often than either HAs or HCs. Equal expression of c-jun occurred in any of the three lesion types. Although these results could be used to argue that no relationship existed between HNs and later-appearing HAs and HCs, those HNs that were marker positive contained small nests of marker-positive hepatocytes among a field of normally appearing unstained hepatocytes. No similar nests of marker-positive cells were detected in any area of normal liver outside the HNs. Also very few altered hepatic foci (AF) were detected with these markers or with hematoxylin and eosin, or with histochemical stains for ATPase or glucose-6-phosphatase deficiencies. These results suggested that these nests within some HNs were areas of transformed, or neoplastic hepatocytes. Phenotypic heterogeneity analysis, in which the number of tumor markers co-expressed by any given lesion was examined, confirmed a significantly greater percentage of HAs and HCs expressing multiple markers than HNs. Those HNs that expressed multiple markers, however, expressed at the same frequency as HAs and HCs and the expression was confined to the same nests of cells. Taken together, these data suggest that these nests of marker-positive cells within the HNs were neoplastic and could develop into later-appearing HAs and/or HCs. The absence of marker expression in normal liver and limited expression in the few AF indicates that the HNs may be the only significant preneoplastic lesion in DCA-induced hepatocarcinogenesis.
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PMID:The role of hyperplastic nodules in dichloroacetic acid-induced hepatocarcinogenesis in B6C3F1 male mice. 186 Jan 58

Among the therapeutic alternatives to orthotopic liver transplantation, hepatocyte transplantation (HT) offers the best potential in a number of liver diseases, mainly inborn errors of metabolism. Nevertheless, HT presents several inconveniences such as the scarce knowledge of the functionality of the transplanted hepatocytes, which has given rise to controversy about the specificity or unspecificity of the transplant, and the lack of a suitable system for preserving the cells. This study was designed to test a system for cryopreserving hepatocytes and to assess their functionality over prolonged periods after their ectopic transplantation. A medium and a freezing schedule which are reproducible and yield elevated viability have been used, and a number of hepatospecific parameters have been assessed: the activity of ornithine carbamoyltransferase--an enzyme of primary importance in the urea cycle--lipogenesis, gluconeogenesis, glucose-6-phosphatase and cytochrome oxidase activities, the presence of albumin--as an index of plasma protein synthesis--and IDA uptake and metabolism, showing the UDP-glucuronyl transferase activity. As dedifferentiation markers, gamma-glutamyl transpeptidase and alpha-fetoprotein have been studied. From the results, it can be deduced that hepatocytes can be cryopreserved and transplanted and that under these conditions they maintain hepatic features for a long time. Following transplantation, several specific liver functions appear or are enhanced in the spleen. Freshly isolated and cryopreserved transplanted hepatocytes have similar behaviors, although a difference in the expression of the function can be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Auxiliary liver by transplanted frozen-thawed hepatocytes. 229 77

Liver carcinogenesis was induced in rats by aflatoxin B1 (AFB1) enhanced by a choline-deficient diet. In Experiment 1, the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), was administered by gavage to one group only during AFB1 administration; another group received DFMO during AFB1 administration and for 2 months after carcinogen administration. These two groups were compared to two control groups, one given AFB1 and fed the choline-deficient diet and another fed the deficient diet only. In a second experiment, DFMO was administered at a concentration of 2% in the water for 3 weeks and then at 1% for the remainder of the study. Rats from each group in Experiment 1 were killed at 2, 8, and 10 months after AFB1 administration and the development of tumors was followed by histology; autoradiography of [3H]thymidine incorporation into DNA; enzyme histochemistry; and alpha-fetoprotein determination. The group given DFMO during AFB1 administration was not significantly different from the AFB1-treated control group at 2 and 8 months after AFB1 administration. However, at 10 months following AFB1 and DFMO administration, the [3H]thymidine-labeling index and glucose-6-phosphatase staining were significantly increased. This group had three animals bearing hepatocellular carcinomas as compared to none in the controls. The group given DFMO for 2 months after AFB1 administration had a significantly depressed growth rate 2 months later, but this difference was not apparent after 8 months. After 10 months, there was a significantly increased [3H] thymidine-labeling index and increased volume fraction of gamma-glutamyltranspeptidase in the AFB1-DFMO-treated group as compared to the controls. DFMO appeared to inhibit growth under some conditions, but if administration was discontinued after AFB1 exposure, it appeared to enhance tumorigenesis. In Experiment 2, where a larger dose of AFB1 was used and DFMO was administered in the water from start to finish of the experiment, DFMO inhibited tumor induction and depressed the appearance of markers examined during carcinogenesis. These data indicate that the regimen used for DFMO administration can markedly affect tumor induction.
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PMID:Effects of the irreversible ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, aflatoxin B1, and choline deficiency on hepatocarcinogenesis. 241 77

Single doses of diethylnitrosamine, N-hydroxy-2-acetylaminofluorene or N-methyl-N-nitrosourea were administered to rats, before or after obstruction of the common bile duct, and liver sections were stained for alpha-fetoprotein, albumin and glucose-6-phosphatase. In these animals, cells expressing hepatocytic traits were not observed in the resulting expanded population of non-parenchymal epithelial cells. A derivation of non-parenchymal epithelial cells with hepatocytic traits from bile ductular cells is not supported, but not completely ruled out, by these findings. In rats with an obstructed bile duct and administered a single carcinogen dose, serum alpha-fetoprotein was slightly increased, to levels comparable with those occurring after a partial hepatectomy. In these rats, and in partially hepatectomized rats, the cellular source of serum alpha-fetoprotein was not apparent, since no alpha-fetoprotein-positive cells were detected in their liver.
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PMID:Bile ductular cells and the phenotypic heterogeneity of the population of hepatic non-parenchymal epithelial cells induced in rats by chemical carcinogens. 242 28

The Solt-Farber protocol, in the absence of an initiating agent, was used to examine the precursor-product relationship between oval cells and hepatocytes in rat liver. The animals were administered 2-acetylaminofluorene (AAF) by gavage for 2 wk combined with partial hepatectomy 1 wk after administering AAF Two dose levels of AAF were used: 9- and 21-mg total dose for animals in Groups I and II, respectively. [3H]Thymidine was administered i.p. to one-half of the animals at Day 6 post-partial hepatectomy. Animals were sacrificed 7, 9, 11, and 13 days after surgery. Only oval cells became labeled on Day 7 in both groups. On Day 9 both labeled oval cells and labeled basophilic hepatocytes were present in Group I, whereas in Group II only oval cells remained labeled. On Days 11 and 13 both oval cells and basophilic hepatocytes were labeled in both groups. The total amount of radioactivity in Group II livers remained the same on Day 9 when only labeled oval cells were present and on Days 11 and 13 when both labeled oval cells and labeled basophilic hepatocytes were present. The calculated half-life for basophilic hepatocytes was about 50 h. The differentiation of oval cells into basophilic hepatocytes was delayed in Group II as compared to Group I, and the higher dose of AAF also induced the formation of both intestinal metaplasia and bile duct formation. In situ hybridization with an alpha-fetoprotein probe showed a strong expression in groups of typical oval cells and in cells arranged in duct-like structures. In addition a transient expression of AFP was also observed in the areas of basophilic hepatocytes 9 to 11 days after partial hepatectomy. Administration of AAF decreased the level of albumin mRNA in preexisting hepatocytes and caused a significant decrease of serum albumin. In contrast, oval cells showed a strong albumin expression, and basophilic hepatocytes formed islands of albumin-expressing cells. Oval cells and the foci of early basophilic hepatocytes lacked glucose-6-phosphatase activity. At Day 13 significant numbers of basophilic hepatocytes were positive for glucose-6-phosphatase. Oval cells were strongly gamma-glutamyltranspeptidase positive, whereas the foci of basophilic hepatocytes were negative for gamma-glutamyltranspeptidase. Only occasionally were transiently gamma-glutamyltranspeptidase-positive hepatocytes observed in basophilic foci. In summary our data indicate that oval cells can differentiate to hepatocytes and may have an important physiological function as a source of major serum proteins when hepatocytes are unable to synthesize these proteins.
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PMID:In vivo differentiation of rat liver oval cells into hepatocytes. 246 57

A rat hepatoma cell line was established from primary culture using RPMI 1640 without supplements. Hepatomas were induced in rats by 0.06% 3'-methyl-4-dimethylaminoazobenzene. An established cell line, FF101, has been maintained as a monolayer for longer than 34 months and subcultured for 42 passages. The population-doubling time was 78 h. The modal chromosome number was 66. FF101 was transplantable, and morphological examination of the transplanted tumors revealed a mixed type of hepatocellular and cholangiocellular carcinoma. FF101 retained the ability to express tyrosine aminotransferase and glucose-6-phosphatase. Also, FF101 synthesized alpha-fetoprotein. FF101-conditioned medium stimulated DNA synthesis and proliferation of several cell lines such as AH66, K562, and BALB/c3T3. The growth-promoting activity of FF101-conditioned medium was abolished by protease, dithiothreitol, acidic treatment, and heating. Gel filtration of conditioned medium on Sephacryl S-200 disclosed the growth-promoting activity at the molecular size of approximately 60,000 Da, and the isoelectric point (pI) was between 5.5 and 6.5. These results suggest that FF101 synthesizes a novel growth factor which has little specificity in both species and organs.
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PMID:Partial purification of a growth factor synthesized by a rat hepatoma cell line established in serum-free medium. 270 52

Cultured hepatocytes from adult Fischer 344 rats were transformed by virion or cloned simian virus 40 (SV40) DNA using the calcium phosphate method. Transformation by SV40 occurred in either serum-supplemented medium or chemically defined medium (CDM). The frequency was greatest in serum-supplemented medium but transformants did not remain differentiated. In contrast, SV40 transformants developed less frequently in CDM, but retained differentiated functions. The frequency of transformation was enhanced by treatments that stimulated cell proliferation, in particular supplementing CDM with epidermal growth factor. Hepatocytes transformed in CDM were epithelial in morphology, secreted albumin, transferrin, hemopexin, and expressed the enzyme glucose-6-phosphatase, all characteristics of normal liver. Transformants did not produce detectable levels of alpha-fetoprotein, a marker of fetal or abnormal liver. We conclude that (a) hepatocytes can be transformed by transfection with SV40 DNA; (b) the frequency of transformation is enhanced by stimulating DNA synthesis; and (c) the transformed cells retain specific functions of normal hepatocytes in situ. Using this system it will be possible to study transformation of hepatocytes by viral and cellular oncogenes and to determine their effects on hepatocellular differentiation.
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PMID:Transformation of rat hepatocytes by transfection with simian virus 40 DNA to yield proliferating differentiated cells. 301 81

PLC/PRF/5, a tissue culture cell line derived from a human hepatocellular carcinoma and producing hepatitis B surface antigen (HBsAg), was studied by immune and enzyme histochemical techniques. HBsAg was demonstrated in the cytoplasm and on the surface of tumor cells. The percentage of HBsAg-positive cells in subculture increased with time until almost all cells expressed HBsAg when the monolayer reached confluence. Similar patterns were found for alpha 1-anti-trypsin and carcino-embryonic antigen, whereas alpha-fetoprotein was observed only in small foci of cells. Hepatitis B core antigen and albumin were not detected. gamma-Glutamyl transferase activity was markedly increased in the tumor cells, whereas adenosine triphosphatase and glucose-6-phosphatase activities were not demonstrable. Patterns of antigenic expression and enzyme phenotype of PLC/PRF/5 cells show remarkable resemblance to those observed in vivo in human hepatocellular carcinoma. Therefore, this cell line may be a useful model to study the control and modulation of both oncofetal antigens and HBsAg.
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PMID:Immune and enzyme histochemical studies of a human hepatocellular carcinoma cell line producing hepatitis B surface antigen. 616 57


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