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)

A series of experiments was performed to investigate the effect of different types of cell proliferation on the development of enzyme-altered preneoplastic hepatic foci in male Wistar rats. Animals were given a single dose of diethylnitrosamine (100 mg/kg body weight). After a 2-week recovery period liver cell proliferation was repeatedly induced by four or eight necrogenic doses of carbon tetrachloride (compensatory cell proliferation), or by four or eight treatments with three different liver mitogens, namely lead nitrate, ethylene dibromide and nafenopin (direct hyperplasia). The carcinogen altered hepatocytes were monitored as gamma-glutamyltransferase positive or adenosine triphosphatase negative foci. The results indicate that compensatory cell proliferation induced by both four and eight carbon tetrachloride treatments enhanced the growth of diethylnitrosamine-initiated hepatocytes to enzyme-altered foci. On the contrary, repeated waves of cell proliferation induced by liver mitogens did not result in any significant number of enzyme-altered foci.
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PMID:Cell proliferation and promotion of rat liver carcinogenesis: different effect of hepatic regeneration and mitogen induced hyperplasia on the development of enzyme-altered foci. 197 Jul 63

The livers of rats given either the peroxisome proliferating hepatocarcinogen di(2-ethylhexyl)phthalate (DEHP) following initiation by 2-acetylaminofluorene (AAF) or the neoplasm promoter phenobarbital (PB) were studied for changes in 8 histochemical properties. Male F344 rats were fed 200 ppm AAF for 7 weeks to induce hepatocellular altered foci, and were then fed diets containing either no chemical, 12,000 ppm DEHP or 500 ppm PB for 24 weeks. In hepatocytes, DEHP increased alkaline phosphatase activity throughout the lobule, but reduced gamma-glutamyltransferase (GGT) activity in periportal hepatocytes. PB, in contrast, increased GGT activity in periportal hepatocytes. In foci that were induced by AAF, DEHP reduced the histochemical activity of GGT and did not increase the number, mean volume or volume % of foci detected by deficiencies in iron storage, glucose-6-phosphatase, adenosine triphosphatase or fibronectin. PB enhanced the expression of all 8 phenotypic abnormalities in foci such that either more profiles were detected or the area of foci was increased.
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PMID:Effects of the peroxisome proliferator di(2-ethylhexyl)phthalate on enzymes in rat liver and on carcinogen-induced liver altered foci in comparison to the promoter phenobarbital. 197 53

The effect of di(2-ethylhexyl)phthalate (DEHP) on diethylnitrosamine (DEN)-initiated preneoplastic liver lesions with expression of gamma-glutamyltranspeptidase (GGTase) and loss of adenosine triphosphatase (ATPase) as well as alterations of hepatic carbohydrate metabolism in male and female Sprague-Dawley rats have been investigated. Two treatment schedules have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic islands and by the biochemical determination of alterations in enzyme activities of liver homogenates and of serum, the last indicating hepatotoxicity. For initiation, a single dose of DEN was given, followed by treatment with various doses of DEHP given three times weekly by gavage for 7 or 11 consecutive weeks. As histochemical enzyme markers, the expression of positive GGTase as well as the deficiency in ATPase were used for identification of liver foci. The weanling female rats (protocol A) were found to be more sensitive to the carcinogenic effect of DEN in view of foci incidence than the mature male rats which underwent partial hepatectomy prior to DEN application. The administration of 200 mg DEHP/kg body wt increased the incidence of ATPase-deficient foci in both male and female rats; however, concentrations of 1000 and 2000 mg DEHP/kg decreased the incidence of liver foci. The number of foci with expression of GGTase was only slightly increased in female rats following a DEHP concentration of 50 mg/kg, and 200 mg/kg body wt. DEHP alone did not induce preneoplastic lesions that could be identified by these two markers. Biochemical investigations indicate that DEHP alters the metabolic pattern in liver. An increase of the NADP-linked enzymes glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme, extra-mitochondrial ICDH as well as an enhancement of NAD-dependent alpha-G3PDH and lactate dehydrogenase were found following DEHP administration. On the other hand the glycolytic enzymes pyruvate kinase (PK) and enolase as well as the gluconeogenetic enzyme fructose-1,6-bisphosphatase (FBPase) were significantly reduced. In protocol B (male rats) the reactions of PK, FBPase and malic enzyme were more altered after DEHP exposure than in protocol A, while the activity of G6PDH was more increased in protocol A. Most enzymes being involved in the carbohydrate metabolism are influenced by DEHP in a dose-dependent manner. There was no increase in serum FBPase activity in both male and female rats after DEHP treatment but a reduction of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase activities was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci incidence in rat liver. 197 36

The relationships between the gross appearance, histologic types, and cytochemical characteristics of hepatocellular neoplasms were studied in B6C3F1 mice given the liver carcinogen diethylnitrosamine either alone or followed by the organochlorine pesticides, 4,4'-dichlorodiphenyltrichloroethane, chlordane, or heptachlor as promoting agents. Hepatocellular neoplasms were categorized according to their cytoplasmic staining properties with hematoxylin and eosin. Acidophilic neoplasms more often displayed increased activity of alkaline phosphatase than did basophilic neoplasms. The activities of glucose-6-phosphatase and adenosine triphosphatase were decreased in both acidophilic and basophilic neoplasms. There was no difference in the activities of these enzymes or gamma-glutamyltranspeptidase between adenomas and carcinomas, although most neoplasms did not display gamma-glutamyltranspeptidase. Chlordane or heptachlor exposure increased the alkaline phosphatase activity in neoplastic cells, but not that of other enzymes. The majority of neoplasms displayed a deficiency of iron accumulation. The macroscopic appearance of neoplasms was closely related to their cytoplasmic staining properties and cytochemical characteristics.
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PMID:Morphologic and cytochemical properties of mouse liver neoplasms induced by diethylnitrosamine and promoted by 4,4'-dichlorodiphenyltrichloroethane, chlordane, or heptachlor. 242 23

The process of chemical hepatocarcinogenesis is characterized by the appearance of preneoplastic lesions showing changes in the expression of various marker enzymes. We have analyzed the phenotype of small preneoplastic foci and expansively growing nodules in liver sections obtained from rats treated with various carcinogens. Changes within the lesions in canalicular adenosine triphosphatase, gamma-glutamyl transpeptidase, NADPH-(cytochrome P-450) reductase, cytochrome P-450 PB2, epoxide hydrolase, and glycogen content were detected by means of enzyme histochemical and immunohistochemical staining procedures. In parallel sections the expression of albumin messenger RNA was investigated by in situ hybridization using a 35S-labeled albumin specific complementary DNA probe. In general, small preneoplastic lesions showed unchanged levels of albumin messenger RNA. In contrast, the expression of albumin messenger RNA was found to be reduced to varying degrees in large hepatic nodules. An expression of alpha-fetoprotein messenger RNA could not be detected in any of the nodules. No direct correlation between the enzyme phenotype of the lesions and the degree in reduction of albumin messenger RNA could be established except that the reduction was most pronounced in nodules which had lost their ability to store glycogen. Since the synthesis and excretion of albumin is a typical function of the differentiated hepatocyte in the adult animal, the observed decrease in albumin messenger RNA expression in large hepatic nodules is in accordance with the hypothesis of a gradual dedifferentiation or retrodifferentiation of the cell population during carcinogenesis. Hyperplastic nodules produced by continuous treatment of rats with 4-dimethylaminoazobenzene showed increased rather than decreased albumin levels. The analysis of albumin messenger RNA expression might therefore be used as a tool to discriminate between nodules of differing biological nature and fate.
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PMID:Expression of albumin messenger RNA detected by in situ hybridization in preneoplastic and neoplastic lesions in rat liver. 242 87

Fischer F344 rats were given a cyclical diet of 0.06% 2-acetylaminofluorene (AAF), which progressively induced oval cell proliferation, cirrhosis and hyperplastic (or neoplastic) nodules. Primary liver tumours developed from 7 months after ceasing the diet. Liver samples taken during and after AAF administration and specimens of primary tumours were processed into frozen sections and examined microscopically for morphological changes in cell populations, stained histochemically for gamma-glutamyl transpeptidase (GGTase) and four phosphatases, and stained by the immunoperoxidase technique for the presence of antigens detected by seven anti-liver cell monoclonal antibodies and monoclonal antibodies to six oncoproteins. During and after AAF treatment several of the anti-liver antibodies revealed foci of aberrantly or heterogeneously-stained cells, although anti-oncoprotein antibodies showed no consistent changes. Foci of cells positive for GGTase and heterogeneous for adenosine triphosphatase (ATPase) were also seen. Nodules invariably showed heterogeneous antigenicity, raised GGTase and abnormal ATPase expression. Primary tumours exhibited varying degrees of positivity, negativity and heterogeneity with the anti-liver monoclonal antibodies, and all were positive for GGTase. Comparison between various parameters and different lesions showed the greatest concordance between nodules and tumours, suggesting that nodules are probably the precursors of malignant tumours in this system.
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PMID:Heterogeneity of hepatocyte antigen expression in rat liver carcinogenesis: concordance between neoplastic nodules and tumours. 253 34

The histochemical changes of gamma-glutamyltransferase (gamma-GT), adenosine triphosphatase (ATPase), glucose-6-phosphatase (G-6-Pase) and ornithine carbamyltransferase (OCT) were studied in diethylnitrosamine (DEN) -induced and enzyme-altered liver cell lesions (Solt-Farber model) in rats. The number of altered liver cell foci tended to decrease after ceasation of 2-acetylaminofluorene (2-AAF); nevertheless, the number and size of the nodules increased rapidly within 20 weeks. The histochemical changes of most of the altered liver cell foci were focused on one or two kinds of enzyme activity (mostly gamma-GT and ATPase); while most of the nodules presented 3 or 4 kinds of histochemical changes, including OCT and G-6-Pase. It is concluded that some of those altered nodules of multi-enzyme changes might develop continuously to become tumors.
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PMID:[A histochemical study of diethylnitrosamine-induced altered liver cells in rats]. 257 Jun 48

Initial stages of hepatocarcinogenesis have been studied in nonoperated and vagotomized animals. As a carcinogenic substance diethylnitrosamine (DENA) has been used. In order to estimate manifestation of the changes, the histochemical method for revealing glucoso-6-phosphatase activity, adenosine triphosphatase and gamma-glutamyltranspeptidase in the liver has been applied. The disturbance of vagus innervation is stated to delay the course of early stages of hepatocarcinogenesis, induced with DENA.
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PMID:[Early stages of hepatic carcinogenesis after vagotomy]. 257 29

An experimental model was designed to study the role of both diethylstilbesterol (DES) and phenobarbitone (PB) singly or in combination, in diethylnitrosamine (DEN) induced hepatic neoplasia. Experimental and control rats were injected DEN (200 mg/kg) or saline, ip. Acute morphological changes were studied at days 1, 2 and 3; and at weekly intervals for 3 wk. Four weeks after DEN pretreatment the experimental and control rats were randomized into various groups and fed DES (T1), PB (T2) or a combination of both DES and PB (T3). Five rats from each experimental group were sacrificed at 10, 20 and 30 wk. Group T3 showed gross nodules with a mean nodule score of 20.5 mm at 20 wk. Nodule score in T1, T2 and T3 at 30 wk were 7, 9 and 34.5 mm respectively. The sequential morphological lesions encountered were clear cell and acidophilic foci; acidophilic, basophilic and mixed nodules. Haemorrhage within the nodules was frequent when DES was administered either alone or in combination with PB. Oval cell proliferation and cholangiocellular lesions were produced in all experimental groups. Foci and nodules generally showed loss of glucose-6 phosphatase, adenosine triphosphatase and invariable presence of gamma-glutamyl transpeptidase and glycogen. A combination of DES and PB as promoter yielded earliest and highest nodule score. This suggests that DES and PB acted synergestically as promoters or that PB caused enzyme induction thereby enhanced the promotive effect of DES.
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PMID:Synergistic promoter effect of diethylstilbesterol & phenobarbitone in diethylnitrosamine induced hepatic neoplasia in rats. 272 21

Rats received 0.1% lead acetate in their drinking water for 3 weeks or for 6 weeks, at which time renal brush border fractions were obtained for measurement of enzyme activity. Renal brush border preparations from Pb2+-exposed rats exhibited statistically significant decreases in the activity of gamma-glutamyl transpeptidase and alanine aminopeptidase after 3 or 6 weeks of treatment. There was an increase in the activity of alkaline phosphatase which was statistically significant after 3 weeks of Pb2+ exposure. The (Na+,K+) adenosine triphosphatase activity and urokinase activity, located in the basolateral membrane fractions, were unchanged by Pb2+ exposure, as were the protein and phospholipid contents of the brush border fractions. The results are compared to those following acute exposure to Pb2+ or Cd2+.
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PMID:Rat kidney brush border enzyme activity following subchronic oral lead exposure. 285 32


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