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)

Development of preneoplastic lesions in the rat liver under the influence of various modifiers was investigated with particular attention to changes in simultaneous expression of altered enzyme phenotype within the lesions (conformity) and proliferation potential. Degree of conformity of marker enzymes such as glutathione S-transferase placental form (GST-P), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, adenosine triphosphatase and gamma-glutamyltranspeptidase was compared with levels of 5-bromo-2-deoxyuridine labeling. After initiation with diethylnitrosamine, rats were administered the hepatopromoter sodium phenobarbital (PB, 0.05%), the antioxidant ethoxyquin (EQ, 0.5%), or a peroxisome proliferator, clofibrate (CF, 1.0%) or di(2-ethylhexyl)-phthalate (0.3%) and killed at week 16 or 32. The PB promoting regimen was clearly associated with increase in the numbers of high conformity class lesions simultaneously expressing three to five enzymes, and elevated proliferation potential. The inhibitor, EQ, in contrast, brought about a time-dependent decrease in conformity so that only 1 or 2 alterations were most commonly observed at week 32. Lesion populations in the peroxisome proliferator- and especially CF-treated cases were characterized by obvious dissociation between degree of conformity and proliferative status. Such treatment-dependent differences were not always correlated with the size of the lesion. The results thus suggested that the conformity and proliferation potential of preneoplastic lesions are dependent on modification treatment. Overall, GST-P was found to be the most reliable marker, although G6PD was less influenced in the peroxisome proliferator cases.
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PMID:Effects of modifying agents on conformity of enzyme phenotype and proliferative potential in focal preneoplastic and neoplastic liver cell lesions in rats. 133 90

The effects of varying the interval of time between initiation with diethylnitrosamine (DEN) and promotion by phenobarbital (PB) on the development of altered hepatic foci (AHF) and hepatomas in female Fischer 344 rats was investigated. The intervals between DEN initiation after a 70% partial hepatectomy and a subsequent 6 month period of promotion by feeding of PB were 1 day, 1 week, 1 month, 2 months, 6 months and 11 months. The number and volume percentage occupied by AHF were determined by quantitative stereologic methods on serial frozen sections stained for the markers gamma-glutamyltranspeptidase (GGT), canalicular adenosine triphosphatase (ATPase), glucose-6-phosphatase (G6Pase) and the placental form of glutathione S-transferase (GST-pi). The number of AHF was greatest when the initiation-promotion interval was only 1 day, and there was a tendency for the number of AHF to decrease as the interval between initiation with DEN and the start of PB promotion was extended. An 11 month delay between initiation and promotion resulted in only 20% fewer AHF than when promotion was begun 1 day after initiation. On the other hand, the volume percentage fraction of AHF did not change when the initiation-promotion interval was increased from 1 day to 2 months. An interval of 6 months roughly doubled the volume percentage fraction, but an interval of 11 months led to a 7- to 8-fold increase in the volume percentage of AHF over that from a 1 day interval. The phenotypic distribution of AHF was significantly lower in relation to certain markers, especially GGT and GST-pi, in those animals only initiated with DEN compared with those initiated with DEN and promoted with PB. When no exogenous promotion was given, there was still a nearly linear increase in both the number and volume percentage occupied by AHF in the liver of rats initiated with DEN. On the other hand, rats subjected to a 1 week interval between DEN initiation and PB promotion exhibited the greatest number of hepatocellular carcinomas 14 months after initiation, compared with other groups. These studies demonstrated a gradually decreasing effectiveness of PB as a promoting agent to stimulate the growth of all AHF initiated by DEN as the interval between initiation and promotion was extended.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Quantitative stereologic study of the effects of varying the time between initiation and promotion on four histochemical markers in rat liver during hepatocarcinogenesis. 196 85

The effect of a single administration of lead nitrate on the activity of gamma-glutamyltranspeptidase (gamma-GT), adenosine triphosphatase (ATPase), the placental form of glutathione S-transferase (GST-P) and adenylate cyclase (AC), four enzymes widely used as phenotypic markers for preneoplasia, was investigated in the liver of male Wistar rats. The results of the histochemical enzymatic staining indicated that an acute treatment with lead nitrate induces the activity of gamma-GT, mainly in the hepatocytes located around zone I of the liver acinus, with a maximum seen between 72-96 hours. On the other hand, the activity of ATPase was found to be severely inhibited at 2-3 days after treatment, as shown by a strong decrease in the staining of the bile canaliculi of zones II and III. Immunohistochemical analysis revealed that lead nitrate administration also resulted in the appearance in most of the hepatocytes of GST-P, an enzyme whose activity is almost undetectable in normal rat liver, but is elevated in preneoplastic liver lesions. Finally, lead nitrate treatment resulted in an inhibition of AC activity which was maximal after 24 hours.
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PMID:Modulation of the activity of hepatic gamma-glutamyl transpeptidase, adenosine triphosphatase, placental glutathione S-transferase and adenylate cyclase by acute administration of lead nitrate. 290 38

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

Sulphur is an essential micronutrient required by the body in low concentrations, but its high intake can lead to a serious health hazard. Sulphur compounds are reported to induce several toxic responses in animals, but so far no reports are available on the toxic effects of elemental sulphur, following dietary supplementation. The present investigation was carried out with the aim of providing an insight into the role of dietary supplementation of sulphur on the induction of altered hepatic foci (AHF) using medium term liver bioassay in Wistar rats. Induction of AHF are early neoplastic changes in rat liver in diethylnitrosamine (DEN)-initiated and 2-acetylaminofluorene (2-AAF)-promoted hepatocarcinogenesis. The role of sulphur on induction of AHF was evaluated by the development of negative enzymatic foci for alkaline phosphatase (AlkPase), adenosine triphosphatase (ATPase), glucose-6-phosphatase (G-6-Pase) and positive foci for marker enzymes, gamma-glutamyl transferase (GGT), placental isozyme of glutathione-S-transferase (GST-P). A significant dose-dependent decrease in the relative and absolute liver weight of sulphur-administered rats was recorded. Dietary supplementation of 2% and 4% sulphur significantly induces both negative and positive focal areas in terms of area and counts for AHF. However, 1% sulphur administration failed to induce AHF up to significant levels. The results thus revealed the possible tumorigenic risk associated with the high sulphur-containing diet.
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PMID:Induction of preneoplastic altered hepatic foci following dietary sulphur supplementation. 1522

Diallyl sulphide (DAS) is a sulphur-containing volatile compound present in garlic (Allium sativum). It has been shown to inhibit a number of chemically induced forms of cancer in experimental animals. The present study demonstrates the inhibitory effect of DAS on the development of diethylnitrosamine (DEN) initiated and 2-acetyl-aminofluorene (2-AAF) promoted preneoplastic altered hepatic foci (AHF) in Wistar rats. AHF were scored and analysed by quantitative stereology using the Image Analysis system from frozen liver sections stained for biological markers, namely glutathione S-transferase, placental form (GST-P), gamma-glutamyl transpeptidase (GGT), adenosine triphosphatase (ATPase), glucose-6-phosphatase (G6 Pase) and alkaline phosphatase (AlkPase). DAS-supplemented rats were found to restore the near-normal levels of enzymes GST-P and GGT when exposed to DEN and 2-AAF. DAS administration following DEN and 2-AAF exposure led to the restoration of enzymic activity of ATPase, G6 Pase and AlkPase, as evident by number and area of the foci. These findings suggest the protective role of DAS in rat hepatocarcinogenesis, by suppressing DEN- and 2-AAF-induced AHF development.
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PMID:Modulation of altered hepatic foci induction by diallyl sulphide in Wistar rats. 1555 53

Indole-3-carbinol (I3C) is a cleavage product of glucobrassicanin, a natural compound present in a wide variety of plant food substances including members of the family Cruciferae. I3C is known to possess cancer-chemopreventive potential in various animal models. The present study reveals the protective effect of I3C on the development of diethylnitrosamine (DEN)-initiated and 2-acetylaminofluorene (AAF)-promoted preneoplastic, altered hepatic foci (AHF) in Wistar rats. I3C was given at dose levels of 0.5 and 1 mg/kg body weight for five consecutive days along with DEN and AAF. AHF were scored and analyzed by quantitative stereology using the Image Analysis System from frozen liver sections stained for positive and negative biological markers of AHF, that is, glutathione S-transferase (GST-P), gamma-glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase), and alkaline phosphatase (AlkPase). Results revealed the chemopreventive effect of I3C on the DEN-initiated AHF in Wistar rats. The expression of G6Pase, ATPase, and AlkPase was restored in the I3C-supplemented animal. Similarly the induced expression GST-P and GGT also decreased in the animals with I3C administration. The recovery of altered levels of these biomarkers was of comparatively higher magnitude in the animals given a higher dose of I3C (1 mg/kg body weight) in comparison with the animals given 0.5 mg/kg body weight dose of I3C, although no dose-dependence pattern was recorded in I3C-supplemented groups. These results thus suggest the chemopreventive effect of I3C in rat hepatocarcinogenesis by suppressing DEN- and AAF-induced AHF development.
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PMID:Chemopreventive effect of indole-3-carbinol on induction of preneoplastic altered hepatic foci. 1562 69