Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The behavior of hyperplastic nodules following an in vivo short-term screening test for hepatocarcinogens was studied. Rats were injected ip with 200 mg/kg body weight of diethylnitrosamine (DEN), given basal diet containing 200 ppm of N-2-fluorenylacetamide (2-FAA) (group 1), 1000 ppm of the alpha-isomer of 1,2,3,4,5,6,-hexachlorocyclohexane (alpha-BHC) (group 2) or basal diet (group 3) from week 3 to week 8, and then given basal diet and tap water. They were subjected to partial hepatectomy at the end of week 3. Animals were killed at weeks 4, 6, 8, 10, 20, 30, 40, and 50. A significant disappearance of hyperplastic nodules following the cessation of carcinogen treatment was observed in group 1, but was not evident in groups 2 and 3. With gamma-glutamyltranspeptidase (GGTase) as a positive marker and adenosine triphosphatase (ATPase) as a negative marker, hyperplastic nodules were classified into 3 different phenotypic categories, i.e., (1) GGTase-positive and ATPase-negative, (2) GGTase-positive, and (3) ATPase-negative. The percentages of GGTase-positive and ATPase-negative hyperplastic nodules were almost 80 approximately 90% in group 1 and 70 approximately 80% in groups 2 and 3. Some of the hyperplastic nodules were necrotic from week 8 in groups 1 and 2, and from week 20 in group 3. Subsequently, the numbers of necrotic hyperplastic nodules increased with time. Hepatocellular carcinomas were found at weeks 30, 40, and 50 in group 1, and at weeks 40 and 50 in group 2. Significantly higher incidences of cancer were found in group 1 than in group 2. The hepatocellular carcinomas were also classified enzyme-histochemically into 3 different phenotypic categories as for hyperplastic nodules, but the percentage (20%) of GGTase-positive and ATPase-negative hepatocellular carcinomas was significantly lower than that (70 approximately 90%) of GGTase-positive and ATPase-negative hyperplastic nodules in each group.
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PMID:A sequential quantitative study of the reversibility or irreversibility of liver hyperplastic nodules in rats exposed to hepatocarcinogens. 611 91

The activity of plasma membrane marker enzymes which are involved in purine metabolism (5'-nucleotidase, alkaline 5'-nucleotide phosphodiesterase), in active ion transport (Na-K-Mg-adenosine triphosphatase, ouabain-sensitive Na-K-adenosine triphosphatase), in aminoacid transport (gamma-glutamyltranspeptidase), and in basic physiologic functions (alkaline phosphomonoesterase) were assayed in mononuclear cells isolated from peripheral blood of normal donors and of patients with primary immunodeficiency. Irrespective of the clinical classification of the immunodeficiency, the cells of patients were characterized by significantly diminished 5'-nucleotidase and to a certain extent by lower alkaline phosphomonoesterase activities. Average activity levels of other enzymes were similar in cells of patients and controls, but scattering was more pronounced in the first group. Determination of substrate affinity revealed different kinetic properties of 5'-nucleotidase in cells from patients and normal donors; however, the extent of inhibition by beta-glycerophosphate or alpha, beta-adenosine-methylene diphosphate was comparable for both types of cells. The presence of inhibitory compounds in patients' serum was excluded by mixing experiments. When activities of the various plasma-membrane-associated enzymes were compared with each other, significant correlations emerged in normal lymphocytes. Most of these correlations were absent in cell membranes of immunodeficient patients. The findings indicate that the plasma membrane of lymphocytes from patients with immunodeficiency may be characterized by an altered distribution of enzymatic constituents.
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PMID:Correlations between enzymatic and immunologic properties of human peripheral blood mononuclear cells. I. Ectoenzymes of normal and immunodeficient peripheral blood mononuclear cells. 612 61

The hypothesis that during the promotion phase of carcinogenesis a second rare event leads to a promoter-independent tumour cell was tested in an initiation-promotion-initiation type of experiment. Precancerous (island) cells induced in rat liver by 10 mg/kg N-nitrosodiethylamine given 24 h after partial hepatectomy were promoted by a protocol consisting of 2-acetylaminofluorene/partial hepatectomy. Administration of 25-100 mg/kg N-ethyl-N-nitrosourea served as second initiater. Microscopic foci of neoplastic cells were observed within the precancerous islands 66 days later; no such foci were noted in the appropriate controls. Deficiency of adenosine triphosphatase and glucose-6-phosphatase marker enzymes in the foci was more pronounced than in the surrounding island cells; glycogen storage was decreased and cytoplasmic basophilia slightly increased; gamma-glutamyltranspeptidase staining was negative or decreased with respect to the surrounding island cells, which exhibited a partially positive reaction. We conclude that a secondary change produced by N-ethyl-N-nitrosourea in precancerous island cells leads to focus-forming cells which grow, in the absence of promoter, into foci of neoplastic phenotype. Similar rare, initiation-like events might be involved in the process of tumour promotion in general.
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PMID:Initiation-promotion-initiation. Induction of neoplastic foci within islands of precancerous liver cells in the rat. 653 10

The effects of chronic alcohol consumption on nitrosamine metabolism in vivo, DNA synthesis and repair, and carcinogen-induced preneoplasia were studied in rat liver. Following a single injection of different doses of 14C-N-nitrosodimethylamine, there was no significant difference between controls and ethanol-pretreated rats in the alkylation pattern of cellular protein nor in the levels of the alkylation products 7-methylguanine and O6-methylguanine isolated from liver DNA. O6-Methylguanine-specific DNA repair was also unchanged. An increase in the number and size of foci staining negative for adenosine triphosphatase and/or positive for gamma-glutamyltranspeptidase was observed in rats treated intermittently with ethanol and N-nitrosomorpholine. The numbers of clear-cell and mixed-cell foci were also increased. An ethanol-mediated enhancement of DNA synthesis, which was ascertained by different methods, may be related to this cocarcinogenic action of the alcohol. Ethanol, however, failed to demonstrate promoting activity. Long-term treatment of carcinogen pretreated rats with ethanol, according to the classical initiation-promotion protocol, had no effect on the incidence of preneoplastic foci in liver.
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PMID:The mechanism of cocarcinogenic action of ethanol in rat liver. 653 12

Among the proto-oncogenes examined by northern blot analysis, c-myc, c-Ha-ras, c-fos, and c-raf-1 have been reported to be activated in rat liver cell carcinomas. However, there are relatively few reports on protooncogene expression in altered hepatic foci (AHF) early during hepatocarcinogenesis in the rat. In this study, diethylnitrosamine (DEN) at doses ranging from 10 to 200 mg/kg was used to initiate and phenobarbital (0.05%) to promote AHF in rats. AHF were detected by the presence of the marker enzymes glutathione s-transferase, placental form (GST-P); gamma-glutamyltranspeptidase (GGT); glucose-6-phosphatase (G6Pase); and canalicular adenosine triphosphatase (ATPase). Proto-oncogene expression in individual AHF was investigated by in situ hybridization (ISH). ISH for the mRNAs of c-Ha-ras, c-fos, and c-raf-1 revealed little or no expression in AHF. However, the levels of c-myc mRNA were increased in about 10% of the AHF initiated by the highest dose of DEN (200 mg/kg). Thus, altered expression of proto-oncogenes was not seen in AHF initiated by nonnecrogenic doses of DEN and promoted by phenobarbital. However, at the necrogenic dose of 200 mg/kg DEN, c-myc expression was found mostly in AHF in which abnormal expression of GST-P, GGT, G6Pase, and ATPase was also present, indicating that c-myc expression is correlated with phenotypically greater complexity of the AHF, a characteristic of malignant hepatic neoplasms in the rat.
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PMID:Expression of c-myc in altered hepatic foci induced in rats by various single doses of diethylnitrosamine and promotion by 0.05% phenobarbital. 757 7


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