Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 antihistamine methapyrilene was examined for its ability to initiate hepatocarcinogenesis in rats. Rats were first subjected to partial hepatectomy and then were intubated with one of four doses (30, 100, 200 or 300 mg/kg) of methapyrilene hydrochloride (or an equivalent amount of water for controls, or 10 mg diethylnitrosamine/kg for positive controls). Rats were then fed 0.05% phenobarbital in the diet for 3, 6 or 9 months. The number and volume of altered hepatic foci were quantified with the histochemical markers gamma-glutamyl transpeptidase, glucose-6-phosphatase, and ATPase. The number of foci induced was increased 2- to 4-fold by the highest dose of methapyrilene at all 3 time points, but the only statistically significant increase was produced by the 200 mg/kg dose after 3 months of promotion. This study shows that methapyrilene may act as a weak initiator.
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PMID:Effect of the antihistamine, methapyrilene, as an initiator of hepatocarcinogenesis in female rats. 256 26

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

Three rat liver foci bioassays have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic foci, and by the biochemical determination of alterations in enzyme activities of serum indicating hepatotoxicity. We studied the initiation/promotion schedules according to Oesterle and Deml (A), and according to Pereira (B, Broad Spectrum Protocol), and the initiation/selection protocol according to Tatematsu et al. (C), with diethylnitrosamine (DEN), given as a single initiating dose of 10 and 30 mg/kg body wt respectively. With all schedules Sprague-Dawley rats, either females, 3 weeks old (A), or males, 6 weeks old (B, C) were used. For promotion polychlorinated biphenyls (A) or phenobarbital (B) were administered. Selection was performed with 2-acetylaminofluorene (C). The rats in schemes (B) and (C) underwent partial hepatectomy one day prior to initiation. The number and total area of foci deficient in adenosine-5'-triphosphatase (ATPase) and positive in gamma-glutamyltranspeptidase (GGTase) was evaluated. In the complete schedule with 30 mg of DEN in system (A) foci incidence exceeded that of the other systems by about 7-fold (ATPase) and 2-fold (GGTase) respectively. The lower dose of DEN and all control experiments resulted in a respective lower foci yield. With scheme (C), but not with schemes (A) and (B), e.g. serum fructose-1.6-bisphosphatase and alkaline phosphatase were increased, suggesting liver cell damage. Thus tested with DEN, scheme (A) is most sensitive and causes a low impairment of animals' welfare.
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PMID:Comparison of three rat liver foci bioassays--incidence of preneoplastic foci initiated by diethylnitrosamine. 257 25

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

A considerable body of evidence suggests that the nephrotoxic potential of aminoglycoside antibiotics may be associated with the degree of membrane binding and subsequent membrane damage in the renal tubules. In this study, we isolated functional basolateral and luminal membrane vesicles from rat renal cortex, incubated each membrane type in the presence of 1 mM concentrations of either neomycin, netilmicin, gentamicin, hydroxygentamicin, or amikacin, and monitored the activities of the marker enzymes alkaline phosphatase (ALP) and lambda-glutamyltransferase (GGT) (luminal) or ouabain-sensitive Na+,K+-ATPase (basolateral) to determine if there were any selective drug-related alterations of enzyme activities. While none of the five aminoglycosides had any substantive effect upon enzyme activities of luminal vesicles, all five drugs inhibited the basolateral marker enzyme. Neomycin produced the greatest inhibition, hydroxygentamicin and amikacin the least, and gentamicin and netilmicin were intermediate in the inhibition of the enzyme. These results are in accordance with the known relative nephrotoxicity of these same drugs and indicate the usefulness of isolated renal membrane vesicles for in vitro toxicological studies of novel aminoglycosides.
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PMID:Selective membrane toxicity of aminoglycoside antibiotics in membrane vesicles isolated from proximal renal tubules of the rat. 257 75

A comprehensive survey of 11 peptidases, all of which are markers for renal microvillar membranes, has been made in membrane fractions prepared from pig choroid plexus. Two fractionation schemes were explored, both depending on a MgCl2-precipitation step, the preferred one having advantages in speed and yield of the activities. The specific activities of the peptidases in the choroid-plexus membranes were, with the exception of carboxypeptidase M, lower than in renal microvillar membranes: those of aminopeptidase N, peptidyl dipeptidase A ('angiotensin-converting enzyme') and gamma-glutamyltransferase were 3-5-fold lower, those of aminopeptidase A and endopeptidase-24.11 were 12-15 fold lower, and those of dipeptidyl peptidase IV and aminopeptidase W were 50-70-fold lower. Carboxypeptidase M had a similar activity in both membranes. Alkaline phosphatase and (Na+ + K+)-activated ATPase were more active in the choroid-plexus membranes. No activity for microsomal dipeptidase, aminopeptidase P and carboxypeptidase P could be detected. Six of the peptidases and (Na+ + K+)-activated ATPase were also studied by immunoperoxidase histochemistry at light- and electron-microscopic levels. Endopeptidase-24.11 and (Na+ + K+)-activated ATPase were uniquely located on the brush border, and the other two peptidases appeared to be much more abundant on the endothelial lining of microvessels. Dipeptidyl peptidase IV and aminopeptidase W were also detected in microvasculature. Pial membranes associated with the brain and spinal cord also stained positively for endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A. The immunohistochemical studies indicated the subcellular fractionation did not discriminate between membranes derived from epithelial cells (i.e. microvilli) and those from endothelial cells. The possible significance of these studies in relation to neuropeptide metabolism and the control of cerebrospinal fluid production is discussed.
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PMID:Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid. 265 79

Critical parameters in the quantitation of altered hepatic foci (AHF) developing during multistage hepatocarcinogenesis in the rat include: 1) the enumeration of AHF induced by test agents as well as those AHF occurring spontaneously in livers of untreated animals; 2) the volume percentage or fraction of the liver occupied by all AHF as a reflection of the total number of altered cells within the liver and the degree of tumor promotion which has occurred; and 3) the phenotype of individual AHF as determined by multiple markers with serial sections. These parameters, especially the number of AHF, should be corrected by the presence of spontaneous AHF which increase with the age of the animal, more so in males than females. While accurate estimation of the background level of spontaneous AHF can be important in demonstrating that a carcinogenic agent does not possess the ability to increase the numbers of AHF above the background level, a better method to distinguish the effectiveness and relative potencies of agents as initiators or promoters is reviewed. The relative effectiveness of four different markers--gamma-glutamyltranspeptidase (GGT), a placental form of glutathione S-transferase (GST), canalicular ATPase, and glucose 6-phosphatase (G6Pase)--was described for the chemicals C.I. Solvent Yellow 14 and chlorendic acid as promoting agents in males and females. C.I. Solvent Yellow 14 is a more effective promoting agent in females than males, and AHF exhibit extremely low numbers scored by GGT. On the other hand, the numbers of AHF present in livers of male rats promoted by this agent are more than twice those seen in livers of female animals, possibly owing to the effectiveness of this agent as an initiator in the male but not the female. Very few AHF, especially in the male, are scored by GGT during chlorendic acid promotion. The distribution of phenotypes with these markers also differs in the spontaneous AHF appearing in the livers of animals fed 0.05% phenobarbital on either a crude NIH-07 or AIN-76 purified diet. Such studies emphasize the extreme dependence of the promoting stage of hepatocarcinogenesis on environmental factors of sex, diet, and the molecular nature of the promoting agent itself. The hallmark of the final stage of progression in the development of hepatocellular carcinomas is aneuploidy, which may be reflected by phenotypic heterogeneity within individual AHF, termed foci-in-foci. The implications of such quantitative analyses during hepatocarcinogenesis induced by specific agents in relation to the specific action of the agent at one or more of the stages of hepatocarcinogenesis are discussed.
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PMID:Critical parameters in the quantitation of the stages of initiation, promotion, and progression in one model of hepatocarcinogenesis in the rat. 269 39

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

Six groups of F344/N female rats were fed either a modified AIN-76 diet (20% casein, 5% corn oil, 65% cornstarch, 5% cellulose) (AIN) or a diet formulated by Dr. M. Pariza (PD) (30% casein, 10% partially hydrogenated corn oil, 40% sucrose, 15% cornstarch) beginning four days before 70% partial hepatectomy. One day after the surgery, one group fed each diet was intubated with 10 mg/kg diethylnitrosamine (DEN). One week later, these groups plus one control group fed each diet were given 0.05% phenobarbital in the diet for 6 or 14 months. After the rats were killed, blocks of liver tissue were frozen on dry ice and stored at -70 degrees C. Three frozen serial sections were stained for gamma-glutamyltransferase, ATPase, and glucose-6-phosphatase. Numbers and volume of altered hepatic foci (AHF) were analyzed by stereological techniques. After 14 months of feeding these regimens, rats initiated with DEN and fed the AIN + PB had significantly greater numbers and a higher percent volume of the liver of most phenotypes of AHF than all other groups, including those fed PD + PB following initiation with DEN. The numbers of AHF exhibiting more complex phenotypes (i.e., scored by more than one marker) remained unaltered between 6 and 14 months. These findings indicate that the effectiveness of PB as a promoting agent in multistage hepatocarcinogenesis is significantly altered when fed with two different diets of known composition. Therefore, dietary composition can be a significant factor in studies of the stage of promotion in hepatocarcinogenesis.
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PMID:A semipurified diet that suppresses phenobarbital promotion of hepatocarcinogenesis in the rat. 277 2

Sequential carcinogen treatment (diethylnitrosamine/partial hepatectomy followed by 2-acetylaminofluorene (2-AAF] induced multiple hepatocarcinomas in rats with 100% certainty within a year. Enzyme-altered lesions, i.e. gamma-glutamyltranspeptidase (GGT)-positive and/or ATPase-negative cell foci, were numerous already at 8 weeks, and suspensions of purified hepatocytes isolated (by collagenase perfusion) at this time contained 30-40% GGT-positive cells. These hepatocyte suspensions were markedly deficient with respect to autophagic protein degradation (in comparison with cell suspensions from normal rats), and the cells lost less protein and survived much better than normal hepatocytes in culture under conditions of amino acid deprivation (which activates the autophagic mechanism). The anabolic advantage of reduced autophagy may possibly contribute to the selective outgrowth of preneoplastic cells during the earliest stage of liver carcinogenesis. Inclusion of the autophagy inhibitor 3-methyladenine in the culture medium elevated the survival of normal hepatocytes up to the level seen with hepatocytes from carcinogen-treated animals, suggesting that protection of normal cells by autophagy suppression may be a potentially interesting therapeutic principle.
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PMID:Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats. 285 48


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