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 cellular origin of estrogen-induced kidney tumors in male Syrian hamsters has been repeatedly the subject of controversy. Several authors have proposed that the tumors arise from proximal tubules, from a combination of tubular and interstitial stromal cells, or solely from interstitial cells. Because of the model character of this tumor for hormone-associated cancer, it was further investigated in this study with respect to morphology, enzyme and intermediate filament pattern, the expression of alpha-smooth muscle actin and the extracellular matrix proteins fibronectin and tenascin. These analyses were carried out with early and late tumors as well as metastases to determine possible changes in expression of biochemical parameters during the development and progression of this neoplasm. The enzyme histochemical and intermediate filament patterns were usually the same as those described previously for proliferative foci and early tumors, i.e. highly elevated activities of glucose-6-phosphate dehydrogenase, adenylate cyclase and alkaline phosphatase, a lack of glucose-6-phosphatase and gamma-glutamyltransferase and coexpression of vimentin and desmin, alpha-smooth muscle actin could not be detected in early lesions. In five of 24 advanced tumors inclusions of kidney tubules were found which showed various degrees of alteration in their morphology and enzyme histochemical pattern, but were often directly connected with tubular segments of normal appearance outside the tumor. Like the normal tubules, the enclosed tubular segments were strongly positive for cytokeratin but never expressed vimentin or desmin. Among the 24 tumors studied, two contained cysts which expressed cytokeratin and sometimes also vimentin but not desmin. The enzyme histochemistry of the cells lining the cysts was similar to that of the surrounding tumor mass, except adenylate cyclase was lacking and alkaline phosphatase was not uniformly distributed. In tumors containing cytokeratin-positive cysts, there often were cytokeratin-positive, vimentin-negative and desmin-negative tumor formations in close contact to these cysts. With the exception of cyst formation, the pattern of metastases were identical to that of the primary tumors. All large tumors and the main component of the metastases expressed vimentin, desmin and fibronectin. Mesothelia surrounding metastatic tumor complexes were positive for vimentin, desmin, alpha-smooth muscle actin, fibronectin, cytokeratin and tenascin. It was concluded from these and previous observations on early stages of tumor development that the estrogen-induced hamster kidney tumor originates from mesenchymal interstitial cells (probably pericytes) which may rarely acquire an epithelial phenotype by metaplastic transformation during tumor progression.
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PMID:Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters. 171 81

In continuation of earlier studies on murine neoplastic liver lesions, we characterized by histochemical methods the phenotype of hepatocellular adenomas and carcinomas induced by single injections of diethylnitrosamine (1.25, 2.5, or 5.0 micrograms/g of body weight) in 15-day-old C57BL/6 x male C3H F1 mice. The hepatocellular adenomas were composed predominantly of basophilic cells but stored excessive amounts of fat and glycogen in large portions of the tumors. Irrespective of the carcinogenic dose, the adenomas showed a consistent histochemical pattern. Glycogen synthase and phosphorylase were highly active in the hepatocytes that stored glycogen. In cells poor in, or free of, this polysaccharide, these enzymes were only moderately active or even inactive. In glycogen-storing parts of the adenomas, the activity of adenylate cyclase was reduced compared with normal liver parenchyma, but in fat-storing portions it was elevated. In a few adenomas, uniform increase in adenylate cyclase activity could be encountered. The levels of ATPase, acid phosphatase, and glucose-6-phosphatase were either increased or decreased. Glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase showed an increased activity in all adenomas compared with preneoplastic foci, which in turn exhibited a higher glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase activity than the surrounding parenchyma or the liver of untreated controls. The hepatocellular carcinomas showed remarkable histochemical changes compared with adenomas. The levels of fat and glycogen and the activities of glycogen synthase, phosphorylase, and in most cases also that of glucose-6-phosphate dehydrogenase, were reduced significantly. In contrast, adenylate cyclase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase, and also alkaline phosphatase showed a striking elevation in developing carcinomas. Similar, although more pronounced, histochemical changes were seen in the advanced hepatocellular carcinomas. These observations indicated that progression from adenomas to hepatocellular carcinomas was associated with a change in the activity of several enzymes involved in cell membrane function, glycogen metabolism, the oxidative pentose phosphate pathway, and glycolysis.
Cancer Res 1991 Apr 01
PMID:Histochemical profile of mouse hepatocellular adenomas and carcinomas induced by a single dose of diethylnitrosamine. 184 80

Several pharmaceutical agents, manufacturing chemicals, and environmental contaminants were found to act primarily as promoting agents in an initiation-promotion paradigm. The phenotypic distribution of four enzyme markers--placental glutathione-S-transferase (PGST), gamma-glutamyl transpeptidase (GGT), canalicular ATPase (ATPase), and glucose-6-phosphatase (G6Pase)--was analyzed in altered hepatic foci (AHF) by quantitative stereology. The number and volume distribution of AHF were determined for each promoter tested. For phenobarbital and 2,3,7,8-tetrachloro-p-dioxin, PGST and GGT together scored 100% of the AHF; for 1-(phenylazo)-2-naphthol (CI solvent yellow 14) and chlorendic acid, PGST alone marked 90% of the AHF; after chronic administration of WY-14,643, ATP and G6Pase were the predominant markers. In rats fed tamoxifen, G6P scored more than half of the AHF. Differences in the number of AHF promoted by each of these agents and in their phenotypic distributions may reflect the differentially responsive nature of individual initiated hepatocytes to the action of specific promoters. Since the chronic bioassay of suspected carcinogens does not allow one to differentiate between weak complete carcinogens and those carcinogenic agents that act in a reversible manner to promote the growth of previously initiated cells, the partial hepatectomy, altered-hepatic-focus model of cancer development is proposed as a supplement to the chronic bioassay for the identification of those carcinogenic agents that are primarily, if not exclusively, promoting agents in rat liver.
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PMID:An initiation-promotion assay in rat liver as a potential complement to the 2-year carcinogenesis bioassay. 185 24

Renal microsomes isolated on day 3 from cisplatin (CDDP, single i.p. injection, 4 or 6 mg/kg)-treated rats were monitored for their susceptibility to lipid peroxidation as compared with microsomes from rats treated with carboplatin (CBDCA, 30 mg/kg), transplatin (TDDP, 6 mg/kg) or CDDP hydrolysis products (4 or 6 mg/kg) or from control animals. Cephaloridine (1 g/kg daily for 4 days, i.p. injection) was used as a positive control. The effect of CDDP on renal microsomal glucose-6-phosphatase activity was investigated in vivo and in vitro. Following treatment with CDDP and CDDP hydrolysis products vs CBDCA and TDDP treatment, microsomes revealed an enhanced susceptibility to lipid peroxidation in a Fe2+ and/or ascorbic acid stimulation system. Increased lipid peroxidation, expressed as an increase in malondialdehyde (MDA) generation, paralleled the alterations in body and kidney weight and the elevations of plasma creatinine and blood urea nitrogen concentrations. Injection of the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD, 0.5 g/kg, i.p.) at 24 h prior to CDDP treatment abolished the increased vulnerability of renal microsomes to lipid peroxidation. In vivo, only CDDP hydrolysis products exhibited a significant inhibitory effect on renal glucose-6-phosphatase activity. In vitro, rat renal and hepatic microsomal glucose-6-phosphatase activity was decreased by CDDP both time- and concentration-dependently. Nephrotoxicity induced by CDDP and CDDP hydrolysis products might be attributable to iron-dependent lipid peroxidation and microsomes might represent target organelles on a subcellular level.
Cancer Chemother Pharmacol 1991
PMID:Iron- and ascorbic acid-induced lipid peroxidation in renal microsomes isolated from rats treated with platinum compounds. 193 47

Altered hepatic foci (AHF) were analyzed by quantitative stereology on frozen serial sections stained sequentially for gamma-glutamyltranspeptidase (GGT), canalicular adenosine triphosphate (ATPase), glucose-6-phosphatase (G6Pase), and the placental isoenzyme of glutathione S-transferase (GST). Livers for these analyses were obtained from both male and female rats of different ages which had been subjected to initiation with a nonnecrogenic dose of diethylnitrosamine following a 70% partial hepatectomy with subsequent phenobarbital (PB) feeding. Different combinations of these four marker alterations (from single marker to four-marker combinations) were used to analyze the data, and the results were compared for their ability to detect AHF. In rats on the above protocol, GST was the single most effective marker, exhibiting a high sensitivity for scoring both number and volume of foci. There was a high degree of overlap with GGT. The combination of the four different markers, GST/GGT/ATPase/G6Pase, scored 80% more foci in number and 60% more in volume than the routinely used GGT/ATPase/G6Pase method. When all four markers were used to score AHF, PB promotion was equally effective in both sexes at weaning and at 6 months of age, but at 1 year of age males showed a dramatic reduction in the effectiveness of PB as a promoting agent, both for number and volume percentage of liver occupied by AHF. On the other hand, initiation was more effective in the male at weaning and at 6 months of age, although by the 12-month point no distinction between the sexes could be made. When only GGT was used as a marker, promotion by PB appeared to be markedly less effective in males than in females at all ages. In the absence of PB administration, both the number and volume fraction of AHF in the livers of both males and female increased with age. Likewise, both the number of AHF per liver and their volume fractions increased with age in both sexes when uninitiated animals were fed PB, although only after a 6-month lag in females. These experiments demonstrate that the stages of initiation and promotion in hepatocarcinogenesis in the rat as monitored by the number and volume percentage occupied of AHF are altered by both the age and the sex of the animal. The combination of GGT and GST identified all AHF scored by the GST/GGT/ATPase/G6Pase set of markers and thus may be the most efficient combination of markers of AHF resulting from promotion by PB.
Cancer Res 1990 Feb 01
PMID:Quantitative stereological analysis of the effects of age and sex on multistage hepatocarcinogenesis in the rat by use of four cytochemical markers. 196 47

The purpose of this study was to determine the effect of the dietary antioxidant vitamin E on hepatocarcinogenesis by peroxisome proliferators which, it is hypothesized, induce tumors by increased production of hydrogen peroxide or other oxygen radicals. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (10, 50, or 500 ppm) of alpha-tocopheryl acetate for 6 months or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl-transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci were quantified. No tumors or altered hepatic foci were seen at 6 months, but at 21 months the incidence of hepatic tumors and the number and volume of altered hepatic foci were increased in rats fed higher levels of vitamin E. Indices of oxidative damage--concentrations of malonaldehyde, conjugated dienes, and lipid-soluble fluorescence products--were not affected or were lower in rats fed higher amounts of vitamin E; the enhancing effect of vitamin E on the development of altered hepatic foci and hepatic tumors, therefore, was not related to the induction of cellular oxidative damage. Hepatic peroxisomal fatty acid beta-oxidation and vitamin C concentrations were not affected by vitamin E, whereas the glutathione concentration was decreased in rats fed higher amounts of vitamin E. This study shows that increasing the vitamin E content of the diet enhances ciprofibrate-induced hepatocarcinogenesis, but the mechanism of this effect is unclear.
J Cancer Res Clin Oncol 1990
PMID:Effect of dietary vitamin E on the development of altered hepatic foci and hepatic tumors induced by the peroxisome proliferator ciprofibrate. 197 53

The purpose of this study was to determine if the dietary antioxidant selenium could inhibit hepatocarcinogenesis induced by peroxisome proliferators, which are hypothesized to induce tumors by increased production of hydrogen peroxide or other reactive oxygen species. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (0.04, 0.2, or 1.0 ppm) of selenium for 6 or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci at 21 months were lower in rats fed higher levels of selenium (no foci or tumors were seen at 6 mo). Indices of oxidative damage in the liver (thiobarbituric acid reactants, conjugated dienes, and lipid-soluble fluorescence products), however, were not decreased in rats fed the high-selenium diet. Therefore, selenium was protective against ciprofibrate-induced hepatocarcinogenesis, but not by reducing the degree of oxidative damage. The liver selenium and glutathione concentrations, and liver selenium-dependent glutathione peroxidase activity, increased as dietary selenium increased. Therefore, inhibition of carcinogenesis by selenium was correlated with increased levels of glutathione and glutathione peroxidase, but these did not inhibit the indices of oxidative damage. Peroxisomal beta-oxidation also increased with the dietary selenium content; it therefore does not appear to be a factor in the inhibition of hepatocarcinogenesis in rats fed higher levels of selenium.
Nutr Cancer 1990
PMID:Effect of dietary selenium on the induction of altered hepatic foci and hepatic tumors by the peroxisome proliferator ciprofibrate. 208 22

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) was associated with the development of hepatitis, foci of altered hepatocytes and hepatocellular adenomas and carcinomas. The cytomorphological and cytochemical analysis permitted the identification of three different types of focal lesions; namely, glycogen-storage foci, mixed-cell foci and intermediate-cell foci, each showing a characteristic pattern. The cells of the glycogen-storage foci had clear to acidophilic cytoplasm, and were overloaded with glycogen. They showed a marked elevation in the activity of glucose-6-phosphate dehydrogenase (G6PDH) and malate dehydrogenase (MDH), increased activity of succinate dehydrogenase (SDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glycerol-3-phosphate dehydrogenase (G3PDH), reduction in the activity of glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and adenyl cyclase (ADC), and unchanged activity of glycogen synthase (SYN) and gamma-glutamyl transferase (GGT). The mixed-cell foci mainly consisted of basophilic cells poor in glycogen, but were intermingled with cells containing glycogen. These foci were characterized by a marked decrease in activity of PHO, SYN, G6Pase, G6PDH, ATPase and ADC, and increased activity of GGT, SDH, MDH and GAPDH. The intermediate-cell foci consisted of cells with both basophilic and glycogenotic cytoplasmic compartments, and showed a similar enzyme histochemical profile to the mixed-cell foci, with slight differences in the degree of elevation or reduction of some enzymes. The phenotypic similarities and the close spatial relationship between the foci of altered hepatocytes, and the hepatocellular adenomas and carcinomas in WHV-infected woodchucks, suggest that these lesions are preneoplastic. The focal morphological and metabolic aberrations emerging during hepatocarcinogenesis in WHV-infected woodchuck, are in principle similar to those identified in the course of chemical hepatocarcinogenesis in various species. The focal metabolic aberrations apparently represent a general biological response of the liver parenchyma to oncogenic agents and are closely linked to neoplastic transformation of the hepatocytes.
J Cancer Res Clin Oncol 1990
PMID:Phenotypic patterns of preneoplastic and neoplastic hepatic lesions in woodchucks infected with woodchuck hepatitis virus. 215 41

Portacaval shunt (PCS) operations were performed on male inbred SD rats. The activity of liver gamma-glutamyltranspeptidase (GGT) increased a few days after the operation and remained high after several months. However, the activity was only present in periportal areas of liver lobules and was mainly restricted to the endothelial lining cells of periportal blood vessels. Phenobarbital sodium (CAS: 57-03-7) administration did not change the distribution of GGT. The activity of liver glucose-6-phosphatase disappeared in the centrilobular areas a few days after the operation but was present in the periportal areas. The distribution of this activity returned to normal after several months. The capacity of liver cells to store glycogen was significantly decreased following the PCS operation. Morphologic changes in hepatocytes observed after the PCS operation did not show similarities to those seen in preneoplastic livers. The nuclei of the small compact hepatocytes found in the animals with PCS were irregular in shape and stained intensively with hematoxylin and eosin. The large pale-staining cells in the periphery of liver lobes were GGT negative and their nuclei had a normal morphology. Neither morphologic nor histochemical changes consistent with preneoplastic and/or neoplastic stage were observed after 10 months in the liver when the PCS operation was performed on rats having received an ip dose (10 mg/kg) of diethylnitrosamine (CAS: 55-18-5) 2 weeks prior to the operation.
J Natl Cancer Inst 1986 Apr
PMID:Histochemical changes in livers from portacaval-shunted rats. 242 Oct 39

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.
Cancer Res 1989 Mar 15
PMID:In vivo differentiation of rat liver oval cells into hepatocytes. 246 57


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