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)

Oval cells and biliary epithelial cells were isolated from livers of rats fed a choline-deficient diet containing 0.1% ethionine and from normal rat livers, respectively. Nonparenchymal cell suspensions prepared from these livers by collagenase perfusion followed by digestion of undissociated tissue with 0.1% collagenase, 0.1% Pronase, and 0.004% DNase I were separated into six fractions by centrifugal elutriation. Cells in each fraction were characterized histochemically for gamma-glutamyl transpeptidase, peroxidase, alkaline phosphatase, and glucose-6-phosphatase activities, and for albumin and alpha-fetoprotein by immunocytochemical methods. Cells from Fraction 5 of the elutriation procedure had various features predicted for oval cells and were selected for further studies. The cell yield in this fraction, from each preneoplastic liver, was 5.7 X 10(7) cells, 93 +/- 2% of which were gamma-glutamyl transpeptidase positive, 6 +/- 1% peroxidase positive, 61% albumin positive, and 29% alpha-fetoprotein positive. Cells in this fraction have a median diameter of 13.1 micron and are diploid and cycling. The majority of these cells has morphological features characteristic of biliary epithelial cells, although some cells display features intermediate between duct cells and hepatocytes. Nucleic acid hybridization using specific probes revealed that these cells contain albumin and alpha-fetoprotein messenger RNAs, while hepatocytes from normal and preneoplastic liver contain only albumin messenger RNA. Biliary cells obtained from normal livers do not contain albumin messenger RNA. The large-scale purification and characterization of cell populations from preneoplastic livers is an important step in elucidating the cellular derivation of liver tumors.
Cancer Res 1984 Jan
PMID:Isolation of oval cells by centrifugal elutriation and comparison with other cell types purified from normal and preneoplastic livers. 669 43

Kinetics of hepatocarcinogenesis was evaluated in 15-day-old male C57BL/6J X C3HeB/FeJ F1 mice using a nontoxic carcinogenic dose range of diethylnitrosamine (DEN). The carcinogen was injected i.p. once, and the animals were killed according to the protocol. Two studies were carried out sequentially over a period of 4 years. In the first study, groups of mice were treated with 0.625, 1.25, 2.5, and 5.0 micrograms of DEN per g of body weight, and subgroups of eight mice were killed at 10-week intervals, the first at 10 weeks following carcinogenic treatment. The dose-response relationship, transformation probabilities, and the dose versus time to 50% incidence of the early (basophilic foci) and later appearing focal and nodular hepatocellular lesions were evaluated. In the second study, groups of mice were treated with 0.312, 0.625, 1.25, 2.5, and 5.0 micrograms of DEN per g of body weight, and subgroups of 8 to 20 animals were killed at 10, 16, 20, 24, 30, 34, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, and 110 weeks after carcinogenic treatment. The numbers of induced basophilic foci and hepatocellular carcinomas per number of liver cells at risk (transformation probabilities) were used to evaluate dose-response, time-response, and time-dose kinetics. In both studies, the kinetics of hepatocarcinogenesis was evaluated from data plotted on the double logarithmic scale. Regardless of the dose used, DEN induced four distinct morphological entities: basophilic (glucose-6-phosphatase deficient) foci; hyperplastic nodules; hepatocellular adenomas; and hepatocellular carcinomas in all animals. The first study demonstrated a positive dose-response relationship and constancy (k) of the product of single dose (d) and the time to 50% (t50%) incidence (d . tn50% = k) for each of the four morphological entities. The numerical value of the power of time (n) increased from 2.6 to 2.7, 3.4, and 5.7 for the above four lesions, respectively. The second study showed first-order kinetics regarding the induction of basophilic foci and hepatocellular carcinomas. The transformation probability of development of basophilic foci was up to three orders of magnitude greater than that observed for development of hepatocellular carcinomas, suggesting a qualitative difference between these two types of hits. The time-response kinetics showed that the development of basophilic foci and carcinomas was related to the time factor by powers of 2 and 4 for these two lesions, respectively. The time-dose relationship to a fixed number of lesions per number of liver cells at carcinogenic risk showed a negative slope with an n value of 2 for the induction of basophilic foci (d . t28/10(7) = k) and an n value of 4 for the induction of hepatocellular carcinomas (d . t40.08/10(7) = k). The data indicated that at least two critical events are needed for the induction of basophilic foci and at least four events are required for the induction of hepatocellular carcinomas...
Cancer Res 1983 Sep
PMID:Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse. 687 63

Basophilic hepatic foci, nodules, and trabecular hepatocellular carcinomas, collectively referred to as focal hepatic lesions, were induced by single injections of 5.0 micrograms of diethylnitrosamine (DEN) per gram body weight in 15-day-old C57BL/6J X C3HeB/FeJ F1 (B6C3 F1) mice. Groups of eight experimental and eight control mice were killed at 3 days and at 1, 2, 4, 10, 20, 28, 36 and 41 weeks after injection. The only observable acute hepatic toxic effect of DEN, a mild steatosis, was noted at 3 days, but this had disappeared by 7 days following injection. Basophilic foci, composed entirely of altered hepatocytes, were first noted, when very small, at 10 weeks. At later times, some of the foci also contained small collections of proliferated ductules, apparently a result of secondary ingrowth from nearby interlobular bile ducts. The hepatocytes within basophilic foci were characterized by their abundant cytoplasmic RNA, a high nuclear to cytoplasmic ratio (two times greater than normal), which gave them a "crowded appearance," and decreased glucose-6-phosphatase activity. During the course of the study, basophilic foci appeared to increase in size and number. Cytologic anaplasia also became more evident, ultimately culminating in the development of typical trabecular hepatocellular carcinomas by 44 weeks. Invasion of hepatic veins by basophilic foci, first noted at 10 weeks, was prominent by 20 weeks and indicated that many of the lesions manifested this characteristic of malignancy well in advance of the anaplastic features that are also diagnostic of hepatocellular carcinoma. The high growth rates of basophilic foci were confirmed by their greatly increased 3H-thymidine labeling indices, which were 20 times greater than background hepatocytes at 20 weeks following DEN injection. Tumor progression during the course of the study was also suggested by a doubling of labeling indices of hepatocytes in the basophilic foci between 20 to 28 weeks. (The term tumor progression is used in a broad biological sense to encompass any or all of the qualitative and quantitative changes describing the stepwise development of initiated cells to highly malignant neoplasms. This definition differs from the more clinical usage which restricts the process to qualitative changes during the late stages in the development of fully autonomous neoplasms.) An analysis of the number and size of transections through basophilic foci and in some cases, actual reconstructions of the foci from serial sections, indicated that, in aggregate, they grew exponentially between 10 to 36 weeks, with a volume doubling time of 2.5 weeks. The combined morphologic and kinetic data support the view that trabecular hepatocellular carcinomas develop from basophilic foci. Because of their ease of quantitation on conventional H&E stained sections, their rather uniformly spherical shapes, and the high probability of their clonal origin, the induced focal hepatic lesions should provide a useful model for studying tumor growth kinetics during carcinogenesis.
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PMID:Preneoplastic and neoplastic progression during hepatocarcinogenesis in mice injected with diethylnitrosamine in infancy. 687 10

Sequential alterations in enzyme histochemical profiles and reaction of hepatocytes to rapid iron overload were examined in male BALB/c mice during chronic, safrole exposure. At 24 weeks after initiation of safrole treatment, foci of enzyme-altered hepatocytes were noted. These foci were composed of cells showing a decrease in reactivity for glucose-6-phosphatase (Glc-6-Pase) and succinate dehydrogenase (SDH) and an increase for gamma-glutamyl transpeptidase (gamma-Glu-T). In control, iron-loaded mice, the livers were intensely siderotic. In safrole-exposed, iron-loaded mice, foci of iron-negative hepatocytes, varying from a few cells to a lobule in diameter, were initially noted at 24 weeks. Both enzyme-altered and iron-negative foci occurred in the livers of exposed mice at all time periods after 24 weeks. After 36, 52, and 75 weeks of safrole treatment, hepatocellular adenomas were noted with altered enzyme histochemical profiles. Hepatocytes from adenomas were characterized by a decreased staining for Glc-6-pase and SDH and increased staining for gamma-Glu-T and glucose-6-phosphate dehydrogenase (Glc-6-PD). In addition, a few nodules showed a decrease in staining for 5'nucleotidase. In iron-loaded mice, hepatocytes of adenomas showed a decreased to negative reaction for iron when the surrounding parenchyma was siderotic. Hepatocellular carcinomas (HPC) occurred in livers of mice exposed to safrole for 52-75 weeks. The cells of HPC displayed similar enzyme histochemical reactions as cells of adenomas. They were decreased for Glc-6-Pase and SDH activity and increased for gamma-Glu-T and Glc-6-PD. In iron-loaded mice, the HPC cells were negative for stainable iron. Foci, adenomas, and HPC displayed some variability in enzyme histochemical reactions. Variability existed between lesions as well as between cells of the same lesion.
J Natl Cancer Inst 1981 Aug
PMID:Biology of hepatocellular neoplasia in the mouse. II. Sequential enzyme histochemical analysis of BALB/c mouse liver during safrole-induced carcinogenesis. 694 76

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-6-phosphatase 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 activities in two bands originating from extracts of nitrosomorpholine-treated livers.
J Cancer Res Clin Oncol 1982
PMID:Biochemical correlation of glycogen content and activity of some enzymes of carbohydrate metabolism in rat liver during early stages of carcinogenesis. 713 Feb 54

The development of glucose-6-phosphatase (G-6-Pase-)-deficient hyperbasophilic foci was analyzed at 4-week intervals in the livers of CD-1 and C57BL/6J x C3H/HeJ F1 (hereafter called B6C3F1) mice given a single i.p. injection of diethylnitrosamine (DEN) (0.1, 0.2, or 0.4 mumol/g body weight) within 24 hr after birth. Transections of G-6-Pase-deficient foci of hepatocytes were readily discernible in liver sections of DEN-treated mice of either sex at 8 weeks of age. The size and number of these foci per liver increased with time. The occurrence of G-6-Pase-deficient focus transections with diameters as large as 1 mm coincided with the gross appearance of 1-mm gray-white nodules in the livers of male B6C3F1 mice at 16 weeks of age and in females at 32 weeks of age. Transections of all grossly visible hepatic nodules from male and female mice were G-6-Pase deficient and hyperbasophilic; the great majority were diagnosed as mouse hepatomas type A. After a single neonatal dose of DEN, the number and rate of growth of the G-6-Pase-deficient foci and the incidence and rate of appearance of gross hepatomas were greater in the liver of male than in those of female mice. In contrast, the average numbers of G-6-Pase-deficient foci in the livers of male and androgenized female B6C3F1 mice at 36 weeks of age were approximately equal and about twice that observed for the livers of DEN-treated female controls. Quantitation of carcinogen-induced histochemically detectable foci and hepatomas as a function of time provides a useful tool for the analysis of initiation and promotion in the mouse liver.
Cancer Res 1981 May
PMID:Quantitative analysis of the time-dependent development of glucose-6-phosphatase-deficient foci in the livers of mice treated neonatally with diethylnitrosamine. 721 32

An electron microscopic, immunocytochemical, and enzyme cytochemical analysis of the previously established oval cell lines OC/CDE 6 and OC/CDE 22 was performed to characterize the phenotype and differentiation patterns of long-term cultures of oval cells. It was found that alpha-fetoprotein, albumin, and cytokeratin 19 are present in all cultured cells. This indicates that oval cells constitute a population of immature cells expressing features of the antigenic phenotype of both the hepatocyte and bile ductular cell lineages. An electron microscopic examination revealed a gradual alteration in the ultrastructure of oval cells toward hepatocyte-like cells. The majority of the oval cells were positive for glucose-6-phosphatase activity. A particularly striking observation was that oval cells were heterogeneous in terms of peroxisome content. Only about 50% of the oval cells had peroxisomes in the cytoplasm, these cells probably being part of the hepatocyte lineage. The other cultured cells did not reveal catalase activity and probably represented cells committed to the bile ductular cell lineage. An addition of clofibrate to the culture medium resulted in a marked peroxisome proliferation in all oval cells, indicating that oval cells might be able to change their differentiation pathway depending on environmental influence toward the hepatocyte lineage. It is most intriguing that in oval cells with abundant cytoplasm peroxisome proliferation was accompanied by proliferation of the smooth endoplasmic reticulum (this is a morphological marker of mature hepatocytes). Taken together, our findings suggest that within the oval cell lines OC/CDE 6 and OC/CDE 22 cells undergoing a morphological and functional differentiation along the hepatocyte and bile ductular cell lineages are present.
Cancer Res 1995 Mar 01
PMID:Phenotype and differentiation patterns of the oval cell lines OC/CDE 6 and OC/CDE 22 derived from the livers of carcinogen-treated rats. 753 42

Preneoplastic and neoplastic liver cell lesions, induced by EHEN (N-ethyl-N-hydroxyethylnitrosamine) in rats, were investigated to establish the numbers of simultaneously expressed altered enzyme phenotypes within the lesion cells. The lesions were divided into 5 classes on the basis of altered expression in one or more of the following 5 enzymes: glutathione S-transferase placental form, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, adenosine triphosphatase, and gamma-glutamyl transpeptidase. Class 1 lesions contained cells expressing one altered enzyme. Similarly, class 2, 3, 4 and 5 lesions had cells simultaneously expressing 2, 3, 4, and 5 enzyme alterations, respectively. Four histopathological categories of lesions, ACF (altered cell foci) (274 lesions), HN (hyperplastic nodules) (47 lesions), HCC (hepatocellular carcinomas) (99 lesions) and THC (transplanted hepatocellular carcinomas) (5 lesions) were studied. Proliferation potential was assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. The distribution profiles of classes 1 to 5 showed a clear reciprocal change from low class (1 to 2 enzymes) predominance in ACF to high class (4 to 5 enzymes) predominance in HN. Increase of BrdU labeling indices was clearly correlated with progression from HN to HCC. Only a small population of class 5 ACF showed a high BrdU labeling index, indicating particular potential for further development. Thus, the stages of EHEN-induced neoplasia were found to be characterized by gradual increase in the number of altered enzyme phenotypes, with acquisition of proliferative potential being associated with further progression towards malignant conversion.
Jpn J Cancer Res 1993 Dec
PMID:Number of simultaneously expressed enzyme alterations correlates with progression of N-ethyl-N-hydroxyethylnitrosamine-induced hepatocarcinogenesis in rats. 790 86

The pharmacokinetics of two commonly used anticancer drugs, methotrexate (MTX) and 5-fluorouracil (5-FU), were investigated in normal and bilharzial-infested mice. Liver glucose-6-phosphatase activity and antipyrine clearance were used as parameters of liver function. Liver glucose-6-phosphatase activity was significantly reduced in bilharzial-infested mice compared with the normal controls. Bilharzial infestation caused a significant reduction in the elimination (beta) and clearance rate (Cl) of antipyrine, whereas its elimination half-life (t1/2 beta) was increased in comparison with the normal controls. A similar pattern was also obtained after MTX and 5-FU administration in bilharzial mice, compared to controls. These results indicate that hepatic bilharziasis causes a significant reduction in the hepatic clearance and elimination of MTX and 5-FU, whereas their areas under the concentration-time curve were significantly increased. These findings may have to be considered in the treatment of bilharzial cancer patients.
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PMID:Pharmacokinetic profile of methotrexate and 5-fluorouracil in normal and bilharzial-infested mice. 808 9

Treatment of female C57BL/6 x DS-F1 mice with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) neonatally resulted in the development of adenomatous nodules and glucose-6-phosphatase (G-6-Pase) deficient foci at 8 and 6 months of age, respectively. Ovariectomy of these mice at 1 month of age hastened the development and increased the incidences of these lesions. Subcutaneous implantation of estradiol-17 beta (E2) with ovariectomy at 1 month of age markedly decreased the incidences of adenomatous nodules and G-6-Pase deficient foci at 10 or 12 months of age, but subcutaneous implantation of progesterone did not reduce their incidences. Subcutaneous implantation of E2 into ovariectomised mice at 6 months of age resulted in significant decreases in the incidences of adenomatous nodules and G-6-Pase deficient foci at 10 months of age, but implantation of E2 into the spleen of ovariectomised mice of the same age had no effect on their incidences. The present results suggest that E2 suppresses the development of adenomatous nodules and G-6-Pase deficient foci induced in the mouse liver by 3'-Me-DAB by actions on tissues other than the liver.
Br J Cancer 1993 Aug
PMID:Suppression by oestrogen of hepatocellular tumourigenesis induced in mice by 3'-methyl-4-dimethylaminoazobenzene. 839 4


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