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 dose-response characteristics of initiation of hepatocarcinogenesis by diethylnitrosamine (DEN) was investigated in the neonatal female rat by means of the quantitative stereologic estimation of altered hepatic foci (AHF) expressing multiple markers. At 5 days of age, female Sprague-Dawley rats were given a single i.p. dose of DEN (0.1-30 mg/kg body wt) or the vehicle (trioctanoin). The semisynthetic AIN-76A diet was provided to half of the rats in each treatment group, while the remainder received this diet containing 500 mg phenobarbital (PB)/kg for 8 months from weaning until the animals were killed. To ascertain more exactly the dose-response relationship for initiation by DEN, the number, volume percentage and phenotypes of the resulting AHF were determined by quantitative stereological analysis on serial sections of frozen tissue, each stained for one of four markers of preneoplasia. A linear relationship was observed between the dose of DEN (0-30 mg/kg) and the number and volume percentage of AHF detected, with each single marker or the total number of AHF detected when the placental isozyme of glutathione S transferase, gamma-glutamyl transpeptidase (GGT), canalicular adenosine triphosphatase, or glucose-6-phosphatase was used as the marker. For each dose, PB administration increased the number and volume of AHF scored compared with similarly initiated rats that did not receive a promoting stimulus. This was, in part, owing to enhanced GGT expression in AHF with PB administration. Promotion by PB resulted in a distribution of AHF phenotypes altered from that observed in rats not receiving PB. Initiation of AHF in neonatal female rats by DEN was linear with doses from 0 to 30 mg/kg for all four of the phenotypic markers employed. In addition, while PB administration stimulated the growth of all AHF phenotypes, the growth of a subset of AHF that expressed the widest variation in preneoplastic markers was specifically enhanced by PB administration.
Carcinogenesis 1993 Mar
PMID:The effect of the dose of diethylnitrosamine on the initiation of altered hepatic foci in neonatal female rats. 809 61

Although expression of the enzyme gamma-glutamyl transpeptidase (GGT) is the most common phenotypic marker of preneoplastic foci in the livers of carcinogen-treated rats, it is not generally expressed in mouse liver tumors or hepatic foci. However, several carcinogens, including safrole and ortho-azoaminotoluene (OAT), have been reported to induce GGT-positive foci in mice. We asked whether safrole and OAT induce GGT expression in preneoplastic foci or if these compounds select for a distinct set of lesions that can be identified by their GGT-positive phenotype. We treated 12-day-old male and female C57BL/6J mice with N,N-diethylnitrosamine (DEN) (0.20 mumol/g body wt) to initiate hepatocarcinogenesis. From 6 to 24 weeks of age, during the promotion phase of hepatocarcinogenesis, groups of mice were treated with 3,4,5,3',4',5'-hexabromobiphenyl (HBB), safrole or OAT. Additional groups of female mice were ovariectomized at 6 weeks of age with or without subsequent chronic treatment with testosterone. All the animals were killed at 24 weeks of age and serial liver sections were stained for glucose-6-phosphatase (G6Pase) or GGT. Both testosterone and HBB were strong promoters of the development of G6Pase-deficient foci. No GGT-positive foci were observed in animals treated with these agents or with DEN alone. In mice fed safrole or OAT during the promotion period, female mice developed more G6Pase-deficient foci than male mice, and GGT-positive foci were observed. Analysis of serial sections revealed that the G6Pase-deficient foci and the GGT-positive foci were independent populations. The relative number of these two classes of foci varied according to the treatment regimen. In females fed safrole, 7% of the foci in the liver were GGT-positive while in female mice fed OAT, 45% were GGT-positive. In all groups of mice in which we observed GGT-positive foci and in ovariectomized female mice, we noted a third independent population of foci which demonstrated significantly increased expression of G6Pase relative to surrounding normal liver. These data indicate that different treatments during the promotion stage of hepatocarcinogenesis in the mouse may give rise to distinct populations of preneoplastic lesions. Further studies of the molecular events giving rise to these distinct lesions will provide insights into the multiple pathways that result in hepatocarcinogenesis.
Carcinogenesis 1993 May
PMID:Induction of three histochemically distinct populations of hepatic foci in C57BL/6J mice. 809 13

Transferrin receptor (TR) performs the major function of binding and internalizing its specific iron-loaded ligand, transferrin, and its expression is closely linked to the proliferation status of the cell. This study was undertaken to elucidate TR expression in the hyperplastic lesion of hepatocyte in chemically induced hepatic carcinogenesis. The resistant hepatocyte model was chosen for a rat model of carcinogenesis and Sprague-Dawley rats were divided into the following groups: the control groups of normal diet and iron-rich diet with or without hydroxyquinoline and the groups of carcinogen alone and carcinogen plus iron-rich diet with or without administration of hydroxyquinoline. Microscopic changes in the liver, expression of transferrin receptor and glucose-6-phosphatase were studied. The hepatocyte of the control group showed both cytoplasmic and membranous expression of TR. The liver of rats fed on high iron diet accumulated iron and the expression of TR was down regulated by intrahepatic iron accumulation. In the carcinogen administered group the resistant hepatocyte of hyperplastic lesion revealed strong membranous expression of TR and failed to accumulate iron in spite of high iron diet but in contrast the surrounding non-resistant hepatocyte expressed TR in both the membrane and cytoplasm and stored iron when fed on high iron diet. The strong membranous expression of TR is one of the characteristics of the resistant hepatocyte of hyperplastic lesion and it seems to be related to the inability to accumulate iron in spite of a high iron diet.
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PMID:Transferrin receptor expression of the hyperplastic lesions of hepatocyte in experimental hepatocarcinogenesis. 852 44

In order to study the interaction of genetic and hormonal factors during murine hepatocarcinogenesis, we compared the number of liver tumors induced by treatment of 12-day-old mice with N,N-diethylnitrosamine (DEN) (0.05 mumol/g body wt) in intact mice and animals gonadectomized at 8 weeks of age from the three inbred strains, C3H/HeJ (C3H), C57BL/6J (B6), and C57BR/cdJ (BR). At 50 weeks of age, the mean liver tumor multiplicity in intact BR females was 28 +/- 13, while that for intact female C3H and B6 mice was 1.4 +/- 4.7 and 0.5 +/- 1.0, respectively. In ovariectomized mice, the yield of liver tumors was approximately 8-fold higher than in intact C3H (10.3 +/- 7.5) and B6 (4.1 +/- 6.6) females. Only a slight increase (35 +/- 14) was seen in ovariectomized BR females compared to intact BR females. Castration resulted in lower mean tumor multiplicities at 32 weeks of age in the males of all three strains. Intact male C3H, B6, and BR mice had mean liver tumor multiplicities of 61 +/- 34, 7.4 +/- 13, and 26 +/- 18, respectively, while the mean tumor multiplicities in castrated C3H, B6, and BR mice were 24 +/- 14, 0.5 +/- 0.9, and 6.1 +/- 10 tumors per mouse, respectively. The apparent rate of growth of glucose-6-phosphatase-deficient, preneoplastic foci in DEN-treated BR females was significantly higher than in B6 females. The growth rates of hepatic foci in BR and B6 males were similar but foci in BR males were 5-fold more numerous than in B6 males. The high sensitivity of BR females may be due, at least in part, to the failure of ovarian hormones to inhibit the growth of preneoplastic foci and the subsequent development of liver tumors. Since BR males had a larger number of hepatic foci, it is likely that androgens increase the rate of focus formation in BR males.
Carcinogenesis 1996 Feb
PMID:Strain dependent effects of sex hormones on hepatocarcinogenesis in mice. 862 37

Mouse renal cell tumors (RCT) were induced in male CBA male mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH) per kg body weight once a week. After a lag period of two years the kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: Glycogen content, basophilia, and activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and glutamyl-transpeptidase (GGT). RCT displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK LDH) and the pentose phosphate pathway (G6PDH) while negative G6Pase and low SDH activity were observed in these cells. The majority of RCT showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCT. Giant cells were detected in some large RCT. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in giant cells compared with other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in renal cell tumors in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early in carcinogenesis, but studies on earlier stages of renal carcinogenesis are needed to substantiate this assumption.
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PMID:[Enzymic spectrum of preneoplastic and neoplastic changes induced by 1,2-dimethylhydrazine in mouse kidneys]. 874 89

Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. gamma-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by gamma-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver.
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PMID:Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic gamma-ray-irradiation in the rat liver. 884 57

Although 1,25-dihydroxyvitamin D3 has been shown to promote the differentiation of cancer cells and cell lines in vitro, its protective effect against a chemical insult known to induce neoplastic growth in vivo has not been evaluated. The aim of this study was to investigate, in vivo, the influence of the vitamin D status on the early response to an insult known to induce morphological and functional changes leading to hepatocarcinogenesis. The influence of vitamin D status on the susceptibility of rat liver to carcinogenesis was studied after the administration of diethylnitrosamine and 2-acetylaminofluorene, in association with a partial hepatectomy (Solt-Farber protocol), to normal or vitamin D-depleted rats. Preneoplastic foci (gamma-glutamyltranspeptidase-positive and glucose-6-phosphatase-negative) appeared in both groups of animals as early as 1 week after 2-acetylaminofluorene withdrawal and continued to increase during the subsequent weeks. Livers from vitamin D-depleted rats exhibited a significant increase in the number of foci over that observed in normal rats at weeks 1 and 5 after 2-acetylaminofluorene withdrawal. However, the main effect of vitamin D depletion was on focus size, which was found to be significantly greater in vitamin D-depleted rat livers at weeks 2 to 6; focus area (volume fraction) was also found to be consistently larger in livers of vitamin D-depleted rats than in those of normal rats. Labeling of oval cells, a cell compartment possibly associated with the repopulation of the liver parenchyma, was significantly reduced by vitamin D depletion. Control rat livers of both groups showed normal liver histology, and no foci, nodules or oval cells were detected in either group. The present data suggest that vitamin D depletion leads to increased in vivo susceptibility to chemicals known to induce hepatocarcinogenesis. Long-term studies must be conducted to evaluate the effect of vitamin D status on the evolution of preneoplastic foci into frank hepatocellular carcinoma.
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PMID:Influence of the vitamin D status on the early hepatic response to carcinogen exposure in rats. 910 32

Connexin32 (Cx32) is the major gap junctional protein in mouse liver. We have shown recently that the formation of liver tumours in Cx32-deficient mice is strongly increased in comparison with control wild-type mice, demonstrating that the deficiency in gap junctional communication has an enhancing effect on hepatocarcinogenesis. We have now compared the effect of Cx32 deficiency on liver carcinogenesis in two strains of mice with differing susceptibility to hepatocarcinogenesis. Heterozygous Cx32(+/-) females were crossed with male Cx32 wild-type C57BL/6J (low susceptibility) or C3H/He (high susceptibility) mice. Since the Cx32 gene is located on the X-chromosome, the resulting F1 males segregated to the genotypes Cx32(Y/+) and Cx32(Y/-). Genotyping was performed by PCR-analysis using tail-tip DNA. Weanling male mice were i.p. injected with a single dose of N-nitrosodiethylamine and were killed 16, 21 or 26 weeks later. The number, volume fraction and size distribution of precancerous liver lesions characterized by a deficiency in the marker enzyme glucose-6-phosphatase were quantitated. The results demonstrate that Cx32 deficiency only slightly affects the number of enzyme-altered lesions, but strongly enhances their growth, both in the resistant and the susceptible mouse strain, suggesting that decreased intercellular communication results in tumour promoting activity irrespective of the genetic background of the mouse strain used. Since Cx32-deficient C3H/He hybrids were approximately 5-10 times more sensitive than C3H/He hybrids with an intact Cx32 gene, this mouse strain may prove very useful for toxicological screening purposes.
Carcinogenesis 1999 Jul
PMID:The effect of connexin32 null mutation on hepatocarcinogenesis in different mouse strains. 1038 16

Administration of phenobarbital for 5 to 7.5 weeks to aged C3HfB/HeN mice with spontaneous liver tumors produced an enhancement of gamma glutamyl transpeptidase activity in the tumors and a decrease in glucose-6-phosphatase and adenosine triphosphatase activity. Discontinuation of phenobarbital feeding for 5.5 weeks resulted in the loss of gamma glutamyl transpeptidase activity in tumors. These findings of alterations in three membrane-associated enzymes indicate that phenobarbital produces substantial changes in the composition of cellular membranes which may be related to its promoting activity.
Carcinogenesis 1980
PMID:Alteration by phenobarbital of membrane-associated enzymes including gamma glutamyl transpeptidase in mouse liver neoplasms. 1121 52

Gene expression of human ovarian carcinoma cell lines and epithelial ovarian tumors was examined by oligonucleotide microarray for about 6000 human cDNAs. (1) Comparison of gene expression between CDDP-sensitive human ovarian serous adenocarcinoma cell lines and CDDP-resistant cell lines revealed that gamma-glutamylcysteine synthetase, glutathione peroxidase-like protein, dehydrogenase (UGDH), NAD(P)H: quinoneoxireductase, glucose-6-phosphatase, ornithine decarboxylase and dihydrodiol dehydrogenase were associated with a mechanism of CDDP-resistance. Comparison of gene expression between taxol-sensitive human ovarian cell lines and taxol-resistant cell lines showed that up-regulation of 30 kinds of gene expression including MDR and semaphorin E in taxol-resistant cell lines. (2) Comparison of gene expression among serous adenocarcinomas, clear cell adenocarcinomas and non-cancerous ovarian tissues by hierarchical clustering demonstrated that clear difference between carcinomas and non-cancerous ovarian tissues but not obvious difference between serous and clear adenocarcinomas. Genes that were up- and down-regulated specifically in these two types of ovarian carcinomas were further selected by the criteria that difference in the mRNA level by more than 4-fold between tumors and non-cancerous tissues. Tissue type specific alterations of gene expression are likely to play important roles in the carcinogenesis of epithelial ovarian tumors. cDNA microarray is a powerful and high-throughput tool to analyze gene expression of cancer development.
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PMID:[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]. 1192 26


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