Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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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

gamma-Glutamyltranspeptidase (gamma-GT) is known to be increased in putative pre-neoplastic foci but also in the periportal zone I of rat liver under a variety of circumstances not directly related to carcinogenesis. To be able to distinguish between these two instances gamma-GT was studied by enzyme determination in micro-dissections obtained from the two locations and by both histochemical and immunohistochemical staining in serial sections. Altered hepatic foci and alterations in zone I were produced in three models of hepatocarcinogenesis: initiation by N-nitrosomorpholine and tumor promotion by phenobarbital, continuous administration of 2-acetylaminofluorene and continuous administration of methapyrilene hydrochloride. In micro-dissections gamma-GT activity was similarly increased in focal lesions and in zone I after feeding methapyrilene. Histochemically detectable gamma-GT, stained according to Rutenburg et al. (23), was observed both in zone I and in focal lesions. Focal lesions were also ATPase negative and UDP-glucuronyltransferase positive in all three models. gamma-GT in focal lesions could be selectively detected by immunohistochemical staining using antibodies to the rat kidney enzyme and an indirect peroxidase reaction. These findings suggest immunochemical differences between gamma-GT in focal lesions and in zone I.
Carcinogenesis 1986 Sep
PMID:Immunohistochemical differentiation of gamma-glutamyltranspeptidase in focal lesions and in zone I of rat liver after treatment with chemical carcinogens. 287 97

The effect of co-administration of diethylnitrosamine (DEN) and Clophen A 50, a commercial mixture of polychlorinated biphenyls (PCB), on pre-neoplastic enzyme-altered islands in livers of female Sprague-Dawley rats was studied. The islands were identified by the loss of adenosine-5'-triphosphatase (ATPase), emergence of gamma-glutamyltranspeptidase (GGTase) and glycogen storage after fasting. DEN was given p.o. (0.4 or 4 mg/kg body wt respectively) twice a week for 11 consecutive weeks. Clophen A 50 (1 or 5 mg/kg body wt respectively) was given alternatively three times a week for 11 weeks. Four groups of rats each received either DEN or PCBs in the respective doses. Control animals were treated with the vehicle or remained untreated. All animals were killed at week 12. In rats treated with 4 mg DEN/kg body wt approximately 80 ATPase-deficient islands/cm2 were observed. Additional treatment with Clophen A 50 enhanced the island number 3-fold. Treatment with 0.4 mg/kg body wt DEN induced 17 islands/cm2. Additional application of Clophen A 50 enhanced the island number approximately 3-fold. The total island area was enhanced to the same extent in both groups. The island incidence in PCB-treated rats and controls was below 1/cm2 with all markers tested. The results indicate that PCBs may exhibit a co-carcinogenic activity.
Carcinogenesis 1986 Oct
PMID:Enhancing effect of co-administration of polychlorinated biphenyls and diethylnitrosamine on enzyme-altered islands induced by diethylnitrosamine in rat liver. 287 10

Preneoplastic liver lesions were produced in female Wistar rats by low doses of aflatoxin B1 (Model 1: administration of 37.5 micrograms/kg 12 and 24 h after partial hepatectomy; Model 2: continuous application of 3.5 micrograms/kg in tap water daily for 28 days with partial hepatectomy after 14 days. The animals then received sodium phenobarbital, 0.1% in tap water, for 180 to 400 days). In both models numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected enzyme histochemically by their negative ATPase and positive gamma-glutamyltranspeptidase reactions. Immunohistochemically these lesions were also UDP-glucuronyltransferase positive. Increased UDP-glucuronyltransferase adds to permanent alterations of a number of drug metabolizing enzymes observed in a variety of different tumor models. These alterations are responsible for the toxin-resistant phenotype (Faber 1984b). Increased gamma-glutamyltranspeptidase was detected both enzyme histochemically and immunohistochemically; whereas gamma-glutamyltranspeptidase activity was present in both AHF/HN and in periportal areas by enzyme histochemistry, the immunohistochemical method selectively stained gamma-glutamyltranspeptidase in AHF and HN. Immunohistochemically detectable UDP-glucuronyltransferase and gamma-glutamyltranspeptidase are markers of putative precancerous liver lesions which may be useful in the analysis of the prestages of liver carcinogenesis.
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PMID:Increased UDP-glucuronyltransferase and gamma-glutamyltranspeptidase in enzyme-altered rat liver lesions produced by low doses of aflatoxin B1. 287 48

Pectin-induced changes in microflora have been shown to elevate the covalent binding of 2,6-dinitrotoluene (2,6-DNT)-related materials to total rat hepatic macromolecules. Therefore, the effect of diets varying in pectin content on the induction of foci and hepatic tumors induced by 2,6-DNT was studied in male F344 rats. 2,6-DNT (3.0-3.5 and 0.6-0.7 mg/kg/day) was incorporated into NIH-07 (NIH), an open formula cereal-based diet high in pectin content, AIN-76A (AIN), a purified pectin-free diet, or AIN-76A supplemented with 5% pectin (AP). Hepatic foci were scored after histochemical staining for gamma-glutamyl transpeptidase (GGT), canalicular adenosine triphosphatase or glucose-6-phosphatase following administration of test diets for 3, 6 and 12 months. The number of foci per cm3 of liver increased in a dose- and time-department manner following incorporation of 2,6-DNT into test diets with NIH greater than AP greater than AIN. In the NIH diet, 2,6-DNT did not alter the phenotypic distribution of foci. Animals fed control or 2,6-DNT-containing AIN and AP diets had few or no GGT foci throughout the study. Hepatocellular carcinomas and neoplastic nodules were observed only in rats fed NIH containing 2,6-DNT. The concentrations of 2,6-DNT-related material covalently bound to hepatic macromolecules after a single oral dose of radiolabeled 2,6-DNT given after 12 months on the diets increased in control rats and in rats receiving low dose 2,6-DNT in the diet with AIN less than AP less than NIH. These studies show that the carcinogenicity of 2,6-DNT differs depending on whether rats are fed an NIH or AIN (+/- pectin) diet. The results suggest that diet-induced alterations in the covalent binding of 2,6-DNT are not the sole factor in determining the carcinogenic response to 2,6-DNT. Furthermore, unidentified contaminants in cereal-based diets may influence foci and tumor production in rat liver during carcinogen treatment.
Carcinogenesis 1986 Nov
PMID:The effect of diet on 2,6-dinitrotoluene hepatocarcinogenesis. 287 86

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

The effects of the non-12-O-tetradecanoylphorbol-13-acetate type tumor promoter palytoxin on human bronchial epithelial cells was studied in an in vitro serum-free culture system. Unlike the results of previous studies with another tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, palytoxin did not induce squamous differentiation of normal bronchial epithelial cells and was equally cytotoxic for normal human bronchial epithelial cells, a human lung tumor cell line, and human bronchial epithelial cells immortalized by infection with adenovirus 12-SV40 hybrid virus (BEAS-2B cells). Palytoxin did not induce a change in free cytosolic Ca2+ concentration of BEAS-2B cells. The effect of palytoxin on the c-myc mRNA steady state level in BEAS-2B cells was studied: 1 pM palytoxin increased the steady-state level at 12 and 18 h. Furthermore, the induction was accompanied by an increase in [3H]thymidine uptake. Because palytoxin binds to (Na+ + K+)ATPase, the effects of ouabain were compared to the effects of palytoxin. A ouabain-resistant cell line was as sensitive to the growth inhibitory effect of palytoxin as the parent ouabain-sensitive cell line, suggesting different binding sites to the (Na+ + K+)-ATPase for palytoxin and ouabain. Ouabain also increased the steady-state level of c-myc gene expression, but earlier than palytoxin, and the increase in the level of c-myc mRNA was accompanied by a drop in DNA synthesis. These results suggest that palytoxin does not act by growth stimulation, differential cytotoxicity or terminal differentiation of normal versus neoplastic cells which are proposed mechanisms of tumor promotion.
Carcinogenesis 1988 Dec
PMID:Effects of palytoxin or ouabain on growth and squamous differentiation of human bronchial epithelial cells in vitro. 290 1

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

Single cell DNA cytophotometry of ATPase-deficient putative preneoplastic foci in rat liver, induced by a single dose of N-methyl-N-nitrosourea (25 mg/kg or 50 mg/kg) and subsequent phenobarbital feeding (0.05% in the diet), revealed three different types: the majority of foci consisted of an almost exclusive diploid cell population, others showed a preferential tetraploid pattern and a few large foci contained a mixture of di-, tetra- and octoploid hepatocytes. The results of this selective measurement of individual preneoplastic foci in Feulgen-stained 20-microns-thick cryostat sections indicate that not only diploid hepatocytes are a target for the transforming action of a carcinogen, but also tetraploid cells, and that both initiated cell types are capable of expanding as a homogeneous clone. However, clonal homogeneity appears to be lost when foci enlarge. A few preneoplastic foci, heterogeneous with respect to DNA content and endowed with an increased proliferative potential, may represent cell populations at high risk of further development into malignancy.
Carcinogenesis 1986 Jul
PMID:Correlations between ploidy and initiation probability determined by DNA cytophotometry in individual altered hepatic foci. 294 Nov 79


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