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)

Effects of 3,4,3',4'-tetrachlorobiphenyl (TCB) on glucose-6-phosphatase (G6Pase)-altered hepatic foci of N-nitrosomorpholine (NNM)-treated B6C3F1 mice were investigated. TCB was chosen as a selective 3-methylcholanthrene-type inducer and tumor promoter. To initiate hepatocarcinogenesis, mice were treated with NNM (160 mg/l, in drinking water for 7 weeks), as in previous studies with the rat model. After a treatment-free interval of 22 weeks, TCB was administered (5 x 50 mg/kg, every 3 days), and liver foci were analysed 10 weeks after the start of TCB treatment. Unexpectedly, the number of G6Pase-negative and -positive foci per liver was markedly diminished following TCB treatment (to 32% and 57%, respectively). On the other hand, the mean volume of the remaining G6Pase-altered foci was enhanced, owing to an increase in the percentage of foci of large size (greater than 0.5 mm2). Throughout the experimental period of 39 weeks prolonged liver injury due to NNM and TCB treatment was demonstrated by histology and by elevated serum levels of glutamate-oxaloacetate transaminase. The results suggest that (in contrast to the rat system) TCB exhibited opposing effects on liver foci in the mouse model: (a) moderate tumor-promoting effects and (b) cytotoxic effects in NNM-injured liver, leading to decreased numbers of liver foci.
J Cancer Res Clin Oncol 1989
PMID:Tumor-promoting activity and cytotoxicity of 3,4,3',4'-tetrachlorobiphenyl on N-nitrosomorpholine-induced murine liver foci. 254 56

UDP-glucuronosyltransferase (UDPGT) was studied immunohistochemically in hepatic foci and nodules of N-nitrosomorpholine-treated mice. Serial sections were stained for glucose-6-phosphatase (G6Pase). It was found that a high percentage of G6Pase-negative liver foci and nodules were also UDPGT-negative (34%). In addition, G6Pase-negative foci without altered UDPGT phenotype (30%) and UDPGT-negative foci without altered G6Pase phenotype (8%) were detected. G6Pase-positive foci were also present (24%). Interestingly, most G6Pase-positive foci were UDPGT-positive (16%). Some G6Pase-positive lesions without altered UDPGT phenotype were also found (8%). The major phenotype observed in rat hepatocarcinogenesis models (UDPGT-positive/G6Pase-negative foci) was not detectable in the mouse model. These results demonstrate heterogeneous alterations of UDPGTs in mouse hepatic foci. They furthermore suggest marked differences between the mouse and the rat in the regulation of UDPGTs in similarly induced rat hepatic foci.
J Cancer Res Clin Oncol 1989
PMID:Heterogeneous alterations of UDP-glucuronosyltransferases in mouse hepatic foci. 254 57

The effects of oral fructose on hepatocarcinogenesis were investigated with cytomorphological, cytochemical and stereological methods. Carcinogenesis was induced in male Sprague-Dawley rats by application of N-nitrosomorpholine (NNM) for 7 weeks. Afterwards, the animals received fructose in the drinking water (120 g/l) and food ad libitum (group I) or tap water and food ad libitum (group II). The incidence of hepatocellular carcinoma in rats treated with NNM plus fructose was 46% as compared to 24% in animals receiving NNM alone (P less than 0.05). There was no difference in the incidences of other malignancies between the groups (group I: 32.1%, group II: 32.0%). Morphometric evaluation of preneoplastic liver lesions indicated the enhancing effect of the fructose treatment several months before malignant tumors appeared. As early as 6 weeks after treatment the hepatic parenchyma occupied by focal lesions was increased from 6.7% in the animals which had received NNM alone to 8.5% (P less than 0.05) in animals having received NNM plus fructose. This increase was predominantly caused by an increase in glycogen storing foci (P less than 0.0005). In addition, the fructose treatment caused a histochemically detectable increase in the activity of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase in both the hepatocytes of the focal lesions and the surrounding parenchyma. In the NNM plus fructose group the activity of the glucose-6-phosphatase in the foci was frequently approximately equal to the activity in the parenchyma of untreated controls. The striking increase in the activity of this enzyme in the surrounding hepatocytes, however, still sharply demarcated the lesions. The potential mechanisms by which fructose enhances hepatocarcinogenesis are discussed.
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PMID:Enhancement of hepatocarcinogenesis in rats by dietary fructose. 256 39

The antihistamine methapyrilene was examined for its ability to initiate hepatocarcinogenesis in rats. Rats were first subjected to partial hepatectomy and then were intubated with one of four doses (30, 100, 200 or 300 mg/kg) of methapyrilene hydrochloride (or an equivalent amount of water for controls, or 10 mg diethylnitrosamine/kg for positive controls). Rats were then fed 0.05% phenobarbital in the diet for 3, 6 or 9 months. The number and volume of altered hepatic foci were quantified with the histochemical markers gamma-glutamyl transpeptidase, glucose-6-phosphatase, and ATPase. The number of foci induced was increased 2- to 4-fold by the highest dose of methapyrilene at all 3 time points, but the only statistically significant increase was produced by the 200 mg/kg dose after 3 months of promotion. This study shows that methapyrilene may act as a weak initiator.
Cancer Lett 1989 Aug
PMID:Effect of the antihistamine, methapyrilene, as an initiator of hepatocarcinogenesis in female rats. 256 26

17 alpha-Ethylestradiol (EE2) was administered chronically to diethylnitrosamine (DEN)-initiated (200/mg/kg, i.p.) adult ovariectomized Sprague-Dawley rats, by means of Silastic implants at an estimated dose of 90 micrograms/kg/day. Isolated hepatocytes from DEN/EE2-treated animals exhibited a 2- to 3-fold increase in nuclear estrogen receptor (ER) levels throughout the promotion period. Furthermore, approximately 30-40% of the receptor was occupied when quantified by an exchange assay. For all groups the ER had a sedimentation coefficient of approximately 8S for unoccupied ER and a binding affinity for 17 beta-estradiol of 0.25 nM. An ER of lower affinity for estradiol was present in animals initiated with DEN and/or promoted with EE2. The increase in hepatocyte ER was associated with a 5.2-fold increase in gamma-glutamyl transpeptidase and 2.5-fold decrease in glucose-6-phosphatase activity at 20 weeks. EE2 treatment caused a 50% increase in the maximal binding capacity (Bmax) of hepatic epidermal growth factor receptors, but the equilibrium binding constant (Kd) did not change. Modulation of mitotic activity of hepatocyte subpopulations by EE2 treatment was indicated by an increase in the proportion of diploid hepatocytes and an increase in the number of hepatocytes undergoing DNA synthesis. In general, effects on ER, epidermal growth factor receptor, gamma-glutamyl transpeptidase and glucose-6-phosphatase were greater in DEN/EE2-treated animals than in rats receiving only EE2. Modification of receptor pathways associated with hepatocyte growth control, ER and epidermal growth factor receptor, may be contributing factors in the clonal expansion of preneoplastic cells during EE2 promotion of hepatocarcinogenesis.
Cancer Res 1989 Dec 01
PMID:Changes in estrogen receptor, DNA ploidy, and estrogen metabolism in rat hepatocytes during a two-stage model for hepatocarcinogenesis using 17 alpha-ethinylestradiol as the promoting agent. 257 15

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.
Cancer Res 1989 Apr 15
PMID:Partial purification of a growth factor synthesized by a rat hepatoma cell line established in serum-free medium. 270 52

Six groups of F344/N female rats were fed either a modified AIN-76 diet (20% casein, 5% corn oil, 65% cornstarch, 5% cellulose) (AIN) or a diet formulated by Dr. M. Pariza (PD) (30% casein, 10% partially hydrogenated corn oil, 40% sucrose, 15% cornstarch) beginning four days before 70% partial hepatectomy. One day after the surgery, one group fed each diet was intubated with 10 mg/kg diethylnitrosamine (DEN). One week later, these groups plus one control group fed each diet were given 0.05% phenobarbital in the diet for 6 or 14 months. After the rats were killed, blocks of liver tissue were frozen on dry ice and stored at -70 degrees C. Three frozen serial sections were stained for gamma-glutamyltransferase, ATPase, and glucose-6-phosphatase. Numbers and volume of altered hepatic foci (AHF) were analyzed by stereological techniques. After 14 months of feeding these regimens, rats initiated with DEN and fed the AIN + PB had significantly greater numbers and a higher percent volume of the liver of most phenotypes of AHF than all other groups, including those fed PD + PB following initiation with DEN. The numbers of AHF exhibiting more complex phenotypes (i.e., scored by more than one marker) remained unaltered between 6 and 14 months. These findings indicate that the effectiveness of PB as a promoting agent in multistage hepatocarcinogenesis is significantly altered when fed with two different diets of known composition. Therefore, dietary composition can be a significant factor in studies of the stage of promotion in hepatocarcinogenesis.
Nutr Cancer 1989
PMID:A semipurified diet that suppresses phenobarbital promotion of hepatocarcinogenesis in the rat. 277 2

Glucose and lipid metabolism in the brain, liver and in a transplanted tumour were found to be variously altered within 2 to 3 h of administering single doses of the radiosensitizer Ro-03-8799 to normal and tumour-bearing mice. Hepatic lactate and glycerol-3-phosphate (G3P) levels were decreased but those of the ketone body beta-hydroxybutyrate (beta-HOBu) were raised. However, in the tumour, these levels were all enhanced. The lactate levels in brain remained relatively constant but both beta-HOBu and G3P levels were altered in a manner similar to that in the liver. The levels of glucose were approximately doubled in blood, brain and tumour, but whereas tumour G6P levels increased, those in the brain were lowered to below the limits of detection. Hepatic glucose levels were significantly decreased after 1 h but G6P levels were not affected. These changes could neither be related to inhibitory effects on hepatic glucokinase or brain hexokinase activity nor to limiting amounts of ATP in both tissues. However, the activity of glucose-6-phosphatase (G6P'ase) was distinctly raised in the liver and the hepatic glycogen stores were also rapidly lowered. Overall, the results suggest that Ro-03-8799 exerts a stimulatory effect on glucose production in the liver. In both liver and brain the levels of free fatty acids and phospholipids were increased whereas those of esterified fatty acids were lowered. Most importantly, the changes in metabolite levels affect the cellular redox couples; those of the cytosol (lactate/pyruvate; G3P/dihydroxyacetone phosphate (DAP] are directed towards the oxidised state in the liver but to a more reduced state in the tumour. The mitochondrial couple (beta-HOBu/acetoacetate (AcAc)) in both tissues is shifted towards the reduced state. These metabolic changes may result in an increase in the degree of hypoxia in the tumour and may well play an important role in the development of neuropathies.
Br J Cancer 1987 Sep
PMID:Effects on intermediary metabolism in mouse tissues by Ro-03-8799. 282 72

Focal hepatocellular lesions, induced in our infant mouse system (15-day-old B6C3F1 mice) by a single carcinogenic dose of diethylnitrosamine (2.5 or 5.0 micrograms/g body weight), were characterized histochemically using toluidine blue, periodic acid-Schiff, glycogen phosphorylase, glycogen synthetase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, ATPase, gamma-glutamyl transpeptidase, and acid phosphatase. Animals were killed 5, 12, 18, and 24 weeks following diethylnitrosamine treatment. The first focal lesions were observed in mice killed at 12 weeks. All foci showed patchy cytoplasmic basophilia and a slight decrease in the glycogen content. The early foci (12 weeks) showed no change in the levels of glycogen phosphorylase and glycogen synthetase, a strong reduction of glucose-6-phosphatase, and a high increase in glucose-6-phosphate dehydrogenase. In addition, 56% of foci in males and 86% of foci in females showed a slight rise in glyceraldehyde-3-phosphate dehydrogenase, and 12% of foci in males and 17% of foci in females had a lower acid phosphatase. The level of cytoplasmic ATPase was slightly decreased in 22% of foci. By 24 weeks, a decrease in the activity of cytoplasmic ATPase was observed in 84 and 100% of foci in males and females, respectively. The increase in the membrane ATPase was observed in 65% of foci in males and 7% of foci in females. By that time, the decrease in acid phosphatase was observed in 78% of foci in males and 37% of foci in females. The gamma-glutamyl transpeptidase failed to show any increase in its activity, indicating that this enzyme was not a "marker" of the hepatocellular lesions developing under the experimental conditions. Strong decrease in glucose-6-phosphatase in association with a manifest increase in glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activities indicated a shift from gluconeogenesis to glycolysis. Since this metabolic shift occurred concurrently with an increase in the labeling indices and focal size, it appears that these changes act in concert, representing expression of the acquired functional and replicating potential of the focal cell population.
Cancer Res 1985 Jun
PMID:Histochemical characterization of focal hepatic lesions induced by single diethylnitrosamine treatment in infant mice. 285 11

The effect of feeding hypolipidemic peroxisome proliferators on the induction of altered hepatic foci (AHF) in Fischer rats was studied in order to determine whether such agents can induce or promote the development of AHF. In the first study, rats were fed ciprofibrate (10 mg/kg/day) for 1 yr. AHF, neoplastic nodules, and hepatocellular carcinomas were induced. The presence of putative gamma-glutamyltranspeptidase (GGT) activity was numerically the most common marker, although it was absent in larger foci and nodules. A deficiency in canalicular ATPase and glucose-6-phosphatase provided the best markers for the larger foci and nodules. In the second study, rats were subjected to partial hepatectomy, and half of the animals were then intubated with diethylnitrosamine (10 mg/kg). One wk later, rats were fed Wy-14,643 at concentrations of 0, 0.05, and 0.1% in the diet for 6 mo. At 6 mo, the number and volume of foci were increased by the feeding of Wy-14,643 after partial hepatectomy alone and were greatly increased when Wy-14,643 was fed after partial hepatectomy/diethylnitrosamine administration. Canalicular adenosine triphosphatase and glucose-6-phosphatase deficiencies were the most common markers of AHF, and AHF of these phenotypes occupied practically all of the focal volume. The larger AHF did not express GGT, and those foci exhibiting GGT were much less common and occupied very little volume. The absence of the GGT protein itself, as opposed to an inhibition of GGT activity, was verified by immunohistochemical staining using an antibody to GGT. These studies show that hypolipidemic peroxisome proliferators can stimulate an increase in AHF following a single dose of diethylnitrosamine and a mitotic stimulus, and they thus can act as promoters in two-stage liver carcinogenesis. GGT is a poor marker for identifying AHF induced by peroxisome proliferators during the early, premalignant phase of hepatocarcinogenesis.
Cancer Res 1986 Sep
PMID:Induction of altered hepatic foci in rats by the administration of hypolipidemic peroxisome proliferators alone or following a single dose of diethylnitrosamine. 287 87


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