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)

The sequential histochemical changes during colon carcinogenesis were studied in male Sprague-Dawley rats given 16 weekly subcutaneous injections of 15 mg 1,2-dimethylhydrazine per kg body wt and serially killed at regular intervals. Cryostat sections were used to study the mucus content of the colonic mucosa with the periodic acid Schiff's reaction, and enzyme histochemical methods were applied to investigate the activity of some key enzymes of carbohydrate metabolism at different stages of carcinogenesis. Enlarged mucus-rich crypts with a marked hypercellularity (149% of control as determined morphometrically) appearing very early during carcinogenic treatment revealed almost normal activities of glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Hyperbasophilic crypts lacking mucus production were observed later and showed a loss of G6Pase, but marked increase of G6PDH and GAPDH activity. Mucus-rich signet ring cell carcinomas showed the same enzymatic pattern as the mucus-rich crypts, whereas mucus-free adenocarcinomas and undifferentiated carcinomas revealed a loss of G6Pase and highly increased G6PDH and GAPDH activities. The results showed that focal changes in polysaccharide content and in the activity of some enzymes of carbohydrate metabolism, as observed in various organs, also accompany the carcinogenic process in the colon. This supports the concept that aberrations in carbohydrate metabolism play an important role during the process of carcinogenesis.
Carcinogenesis 1987 Jan
PMID:Sequential histochemical and morphometric studies on preneoplastic and neoplastic lesions induced in rat colon by 1,2-dimethylhydrazine. 287 49

Female F344/N rats dosed with diethylnitrosamine (DEN) 24 h after partial hepatectomy were treated with the promoting agents, phenobarbital (PB) or 3,4,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or the peroxisome proliferating agent, WY 14,643, for 6 months. Another group was subjected to the Solt-Farber protocol. Altered hepatic foci (AHF) were analyzed by quantitative stereology from frozen serial sections stained for gamma-glutamyl transferase (GGT), canalicular adenosine triphosphatase (ATPase), glucose-6-phosphatase (G6Pase) and the placental isozyme of glutathione S-transferase (PGST). PGST scored more foci in all groups than GGT and ATPase. PGST marked greater focal volume than GGT or ATPase, and PGST marked focal volume equal to or greater than G6Pase in rats treated with PB, TCDD or the Solt-Farber protocol. However, after treatment with WY 14,643, GGT and PGST marked much less focal volume than ATPase or G6Pase, and PGST scored fewer foci than G6Pase. Numerical estimations of foci scored by those markers on the basis of area of the entire tissue section (per cm2) were relatively different from those values determined by quantitative stereology. While these results confirm earlier studies, they demonstrate the importance of quantitative stereologic analysis of AHF during multistage hepatocarcinogenesis.
Carcinogenesis 1987 Sep
PMID:Quantitative stereological evaluation of four histochemical markers of altered foci in multistage hepatocarcinogenesis in the rat. 288 1

Formation of the N-(deoxyguanosin-8-yl)-aminofluorene adduct was studied in enzyme-altered foci induced by four different liver carcinogenesis models. Foci were detected and scored for enzyme phenotype by a computer-aided image overlay technique. Localization of the enzymes gamma-glutamyl transpeptidase, canalicular ATPase and glucose-6-phosphatase was performed by enzyme histochemistry, allowing identification of foci of seven different phenotypes. Patterns of foci obtained by image overlay were compared to in situ 2-acetylaminofluorene--DNA adduct distribution obtained by immunofluorescence. Foci were induced by the following models: (1) chronic feeding of 0.02% 2-acetylaminofluorene (2-AAF) for 8 weeks; (2) intubation of diethylnitrosamine (DEN) (10 mg/kg) 24 h after a 70% partial hepatectomy (PH), followed 8 weeks later by a diet containing 0.05% phenobarbital for 9 months; (3) intubation of DEN (10 mg/kg) 24 h after PH, followed by a diet containing 0.01% ciprofibrate for 5 months, and after an additional 4 months a diet containing 0.05% phenobarbital for 2 months; (4) maintenance for 7.5, 16.5 or 19.5 months after transplantation of DEN/2-AAF/PH ('Solt-Farber' protocol) donor liver cells into host rats receiving a brief 2-AAF/PH selective regimen then no further treatment until sacrifice. To test the capacity of both foci and morphologically normal livers to form DNA adducts, the animals in models 2-4 received a diet containing 0.02% 2-AAF for 5 or 6 days before sacrifice. In all of the enzyme-altered foci identified in models 1-3 there were no DNA adducts visible by immunofluorescence. Scattered groups of positive cells were occasionally seen in the otherwise dark foci induced by model 4. For technical reasons some enzyme-altered foci were not identifiable on the fluorescence-stained slides. In liver serial sections from rats in models 1-4, there were 75, 304, 125 and 68 enzyme-altered foci of seven different phenotypes which were identified as AF-DNA negative. In models 1 and 4 there were some additional adduct-negative foci not associated with any of the seven identified focus phenotypes. These studies demonstrate that loss of the ability to form DNA adducts in hepatic enzyme-altered foci is a common and very early biochemical adaptation to xenobiotic exposure in different hepatocarcinogenesis models. This adaptation also is retained by the majority of foci in later stages of hepatocarcinogenesis.
Carcinogenesis 1988 Apr
PMID:Lack of acetylaminofluorene--DNA adduct formation in enzyme-altered foci of rat liver. 289 93

Three enzyme makers, glucose-6-phosphatase, ATPase and gamma-glutamyl transpeptidase, have been used in studying carcinogenesis of hepatocellular carcinoma. They have been investigated in animal models and human hepatocellular carcinoma in vivo and in vitro. But the inconsistent levels of these three enzymes associated with this type of carcinoma raised the possibility that the carcinoma cells might have derived from the cells originating from different stages of differentiation. To evaluate this possibility, three human cell lines, Hep G2, Hep 3B, and HA 22T, all thought to be arrested in different stages of differentiation based on their biochemical and morphological characteristics, were used as models. The three enzyme markers glucose-6-phosphatase, ATPase and gamma-glutamyl transpeptidase were examined cytochemically and biochemically. Our results showed that there was no correlation between the ATPase levels and the stages of the cell line's differentiation. But both glucose-6-phosphatase and gamma-glutamyl-transpeptidase were higher in cells that were more differentiated.
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PMID:Cytochemical localization and biochemical analysis of the enzyme markers in human hepatoma cell lines. 290 58

Preneoplastic liver lesions were produced in female Wistar rats by oral administration of 2-acetylaminofluorene for 165 days succeeded by a carcinogen-free standard diet up to 420 days. During the treatment numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected histochemically by a focal decrease or lack of adenosine-5-triphosphatase and glucose-6-phosphatase (G-6-Pase) activities. In addition, the immunohistochemically demonstrable amount of L-type pyruvate kinase was clearly reduced. The histochemically demonstrated decrease of G-6-Pase was substantiated by microbiochemical determination of the enzyme activity in microdissected material. Moreover, during the experimental period a continuous decrease in glucokinase and an increase in hexokinase was detected microbiochemically within AHF and HN. These alterations indicate a shift in the carbohydrate metabolism from gluconeogenesis to glucose utilization and pentose-phosphate-pathway for biosynthesis of nucleic acids. Beside other oncofetal markers, HK may be used as indicator of the early stages of liver carcinogenesis.
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PMID:Decrease in glucokinase and glucose-6-phosphatase and increase in hexokinase in putative preneoplastic lesions of rat liver. 304 Jul 65

We have previously shown that C3H/HeJ male mice are approximately 20-fold more susceptible to the induction of liver tumors by N-ethyl-N-nitrosourea (ENU) than are C57BL/6J male mice and that this difference in sensitivity is largely determined by a single genetic locus (Hcs, hepatocarcinogen sensitivity). In order to determine whether the Hcs locus affects initiation or promotion of hepatocarcinogenesis, we studied the development of putatively preneoplastic hepatic lesions that are deficient in glucose-6-phosphatase (G6Pase) in mice treated at 12 days of age with ENU. In ENU-treated male mice of both strains, the number and size of G6Pase-deficient hepatic foci increased over time between 12 and 24 weeks of age. However, the rate of growth of the lesions was 1.7 times faster for C3H/HeJ male mice (volume doubling time 2.0 +/- 0.7 weeks) than for C57BL/6J mice (3.4 +/- 0.4 weeks). Although the number and size of G6Pase-deficient foci induced by ENU treatment of female C3H/HeJ and C57BL/6J mice were smaller than for foci in similarly treated male mice, there was no significant difference between the growth rates of the foci in female C3H/HeJ and C57BL/6J mice. Thus, the phenotypic effect of the Hcs locus appears to be dependent on promotion of liver tumor induction by the male hormonal environment. In agreement with studies on the growth rate of the foci in male mice, the [3H]thymidine labeling index of G6Pase-deficient hepatocytes in C3H/HeJ males (12%) was 1.5-fold higher than in C57BL/6J male mice (8.0%) at 20 weeks and 1.2-fold higher at 28 weeks (11% versus 9.5%). The labeling index of histochemically normal hepatocytes in C3H/HeJ male mice (0.38%) was 2.6-fold higher than in C57BL/6J mice (0.15%) The Hcs locus may affect the promotion phase of hepatocarcinogenesis in male mice by increasing the proliferative rate of both normal and preneoplastic hepatocytes.
Carcinogenesis 1988 Jun
PMID:Rapid growth of preneoplastic lesions in hepatocarcinogen-sensitive C3H/HeJ male mice relative to C57BL/6J male mice. 337 Jul 54

Adenylate cyclase (AC) activity was demonstrated histochemically using adenylate-(beta,gamma-methylene)diphosphate as substrate in cryostat sections of livers from 45 rats treated for 7-10 weeks with N-nitrosomorpholine (NNM) (120 mg/l drinking water) and from nine untreated control rats. The enzyme patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and correlated with the morphologically defined stages of tumour development in the liver. Light microscopically, the enzyme activity of normal tissue was restricted to the plasma membrane, and was most pronounced along the bile canaliculi of the hepatocytes. In glycogen storage foci and mixed cell foci induced by NNM no, or only very weak, AC activity was visible. In the cells of neoplastic nodules and hepatocellular carcinomas AC activity was also clearly reduced. However, in small parts of the plasma membrane which lined lumina resembling normal bile canaliculi and in cytoplasmic vesicles closely associated with these structures, some AC activity was occasionally detected by light and electron microscopy. Whereas the tissue of normal appearance surrounding the lesions showed a marked increase in AC activity in the presence of glucagon, forskolin and cholera toxin. AC activity in the preneoplastic and neoplastic liver lesions could not, or could only weakly, be stimulated by this treatment. As demonstrated in serial sections of the foci, the reduction in AC activity corresponded to changes in the activity of other enzymes studied earlier in the same model. Thus the reduction in AC activity was accompanied by a decrease in the activity of glucose-6-phosphatase and glycogen phosphorylase, and by an increase in the activity of glucose-6-phosphate dehydrogenase. The results support the concept that the focal changes in the activity of many enzymes (including those of carbohydrate metabolism) during hepatocarcinogenesis are the consequence of aberrations in superordinate regulatory mechanisms of cell metabolism.
Carcinogenesis 1986 Apr
PMID:Loss of adenylate cyclase activity in preneoplastic and neoplastic lesions induced in rat liver by N-nitrosomorpholine. 369 88

The aim of this study was to determine whether a dietary restriction, which significantly decreases body weight gain, also influences the development of diethylnitrosamine (DEN)-induced liver tumours in Swiss mice. At birth, mice were injected i.p. with a single dose of DEN (0.4 mumol/g body wt); negative control mice were sham injected. After weaning the animals received a stock diet either ad libitum (control group) or at 30% restriction (restricted group). A positive control group was fed ad libitum and received phenobarbital (500 p.p.m.) in their drinking water. At 12 weeks of age, glucose-6-phosphatase (G6Pase)-deficient foci were present in the liver of 80% of the control animals but only in 32% of the restricted group. Quantitatively, restricted animals had fewer foci per unit volume liver and these were smaller than in the control animals. By 36 weeks of age, hepatocarcinomas were seen in 100% of the control mice while in the restricted group there were no such malignant lesions and only 32% showed adenomas. The results clearly show that restriction of food intake inhibits promotion and progression of induced liver tumours. Amongst other uses, this model permits the study of the effect of dietary restriction on liver tumours, at an early stage.
Carcinogenesis 1987 Jan
PMID:The influence of food intake on the development of diethylnitrosamine-induced liver tumours in mice. 380 92

Two carcinogenic aromatic amines with different organotropism were tested for syncarcinogenic effects in rat liver in an initiation-promotion experiment. Trans-4-acetylaminostilbene (AAS) and 2-acetylaminofluorene (AAF) were administered as initiators in four doses each either alone or sequentially combined in both orders. The promotion phase was started by partial hepatectomy and continued by adding phenobarbital (250 p.p.m.) to the drinking water for 26 weeks. The number/cm2 of tissue section and average size of hyperplastic foci, glucose-6-phosphatase-deficient and gamma-glutamyl-transpeptidase-positive foci were determined and a total area of lesions calculated during the promotion phase after 18 and 31 weeks, and in the post-promotion phase after 42 and 47 weeks. The synergistic effects of AAS and AAF were clearly more than additive if compared with the sum of the effects exerted by each compound individually. The sequence in which both initiators were administered remarkably influenced the development of lesions. They developed more rapidly and persisted longer in the post-promotion phase when AAS was administered first and AAF second. In the final stage, enzyme altered foci increased in the livers of both combination groups, but to a greater extent in the AAS-AAF group. It is concluded that the two arylamides damage DNA independently. In addition, however, the results suggest that AAS acts predominantly as an initiator, and AAF as a weak initiator and a strong promoter in what is considered the initiation phase of this experiment.
Carcinogenesis 1985 Sep
PMID:Syncarcinogenic effects on the initiation of rat liver tumors by trans-4-acetylaminostilbene and 2-acetylaminofluorene. 402 33

The endogenous synthesis of cholesterol in hepatocyte nodules, induced in male Wistar rats, by a single dose of the hepatocarcinogen diethylnitrosamine followed by a selection procedure, was investigated and was compared with that in surrounding and control tissue. In addition, the activity of enzymes related to carbohydrate metabolism (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphatase and pyruvate kinase), was measured. Hepatocyte nodules showed a striking increase in their capacity for synthesizing cholesterol, in comparison to surrounding and control tissues, and an enhancement in the activity of the pentose phosphate pathway, as indicated by increased activity of glucose-6-phosphate dehydrogenase and of 6-phosphogluconate dehydrogenase, and a concomitant decrease of glucose-6-phosphatase. The stimulation of cholesterol synthesis and of the pentose phosphate pathway was associated with increased incorporation of labelled thymidine into DNA. These data indicate that, among other metabolic disturbances, enhancement of cholesterol synthesis and of the pentose phosphate pathway, is accompanied by an increased proliferative capacity of hepatocyte nodules.
Carcinogenesis 1985 Sep
PMID:Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferating hepatocyte nodules. 402 34


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