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 kinetics of induction and growth of acinar cell lesions has been investigated in rat pancreas after a single dose of the carcinogen azaserine. The time--response relationship was studied in male Wistar-related rats given a single i.p. injection of 30 mg L-azaserine/kg body weight at 18 days of age. Rats were killed between 4 and 78 weeks after treatment and ATPase-stained pancreas sections were quantitatively evaluated for the number and size of acidophilic, ATPase-positive and basophilic, ATPase-deficient foci. The number of acidophilic foci remained constant from 8 weeks onwards, while the number of basophilic foci slightly increased with time. The size of both acidophilic and basophilic foci increased throughout the experimental period. Due to two times higher number/cm3 and faster growth of the acidophilic foci, four times more acidophilic than basophilic focus tissue was present at the end of the experiment. Progression of acidophilic foci to adenomas and carcinomas was occasionally seen at later time points (greater than 34 weeks) in this rat strain. The dose--response relationship was studied in male and female Sprague--Dawley rats given a single i.p. injection of 0-45 mg azaserine/kg body weight at 19 days of age. Rats were autopsied at 17 weeks after treatment, and pancreas sections were quantitatively evaluated after ATPase histochemistry. The relationship between dose and number of foci was linear up to 30 mg/kg azaserine for both acidophilic and basophilic foci in males and females. For each individual dose, the number of foci induced was the same in males and females, and there were two to three times more acidophilic than basophilic foci. The percentage of pancreatic tissue occupied by focus tissue was 1.75 times higher in males, pointing to a higher growth-potential of acidophilic foci in males than in females. The first-order dose--response kinetics indicate that the conversion of a normal acinar cell into a focus-forming cell occurs by one specific azaserine-mediated rare event, occurring probably at the genetic level of the target cell.
Carcinogenesis 1990 Feb
PMID:Kinetics of induction and growth of putative precancerous acinar cell foci in azaserine-induced rat pancreas carcinogenesis. 213 81

The ability of methyl-deficient, amino-acid-defined diets to produce enzyme-altered foci was quantitatively determined in the livers of rats treated both with and without an initiating dose of diethylnitrosamine (DEN). Male weanling F-344 rats were fed a complete, amino-acid-defined diet for 1 week. They were then injected i.p. with a single dose of DEN (20 mg/kg body weight) and fed the complete diet for an additional week. Forty animals in each dose group were then maintained for 5-38 weeks on the complete diet (diet 1) or one of the three methyl-deficient diets customarily used in this laboratory: diet 2, devoid of methionine and choline; diet 3, devoid of methionine only; and diet 4, devoid of choline only. In diets 2 and 3, methionine was replaced by equimolar amounts of its metabolic precursor, DL-homocystine. Ten animals per group were killed 8, 12, 17, 24 and 41 weeks after DEN initiation. For 2 weeks prior to being killed, each group was maintained on the complete diet to minimize the histological abnormalities due to acute toxicity of the diets. Serial sections of the livers were obtained, stained sequentially for gamma-glutamyltranspeptidase, ATPase and glucose-6-phosphatase, and the quantitation of the focal lesions scored by these markers was carried out by quantitative stereology. The results indicated that, regardless of the enzyme marker(s) examined, there was a general correspondence between the volume and number of altered hepatic foci (AHF) formed and the previously described tumor-promoting activities of each diet. Thus, while all DEN-treated groups contained significant numbers of AHF 24 weeks after initiation, only the diet-2-fed animals displayed such foci at 8 weeks. Similarly, among the uninitiated rats, only those fed diet 2 exhibited the presence of AHF throughout the experimental period. Interestingly, the livers of uninitiated, choline-deficient rats showed a small number of AHF at 24 and 42 weeks; these foci were not observed at all in the corresponding DEN-untreated animals fed diet 3, deficient in methionine only. The results provide evidence that the carcinogenic effects of the methionine- and choline-deficient diet result more from its strongly promoting effect than from any initiating activity by the diet.
Carcinogenesis 1990 Feb
PMID:The effect of choline and methionine deficiencies on the number and volume percentage of altered hepatic foci in the presence or absence of diethylnitrosamine initiation in rat liver. 230 54

A number of closely related post-transcriptional facets of RNA metabolism show nuclear compartmentation, including capping, methylation, splicing reactions, and packaging in ribonucleoprotein particles (RNP). These nuclear 'processing' events are followed by the translocation of the finished product across the nuclear envelope. Due to the inherent complexity of these interrelated events, in vitro systems have been designed to examine the processes separately, particularly so with regard to translocation. A few studies have utilized nuclear transplantation/microinjection techniques and specialized systems to show that RNA transport occurs as a regulated phenomenon. While isolated nuclei swell in aqueous media and dramatic loss of nuclear protein is associated with this swelling, loss of RNA is not substantial, and most studies on RNA translocation have employed isolated nuclei. The quantity of RNA transported from isolated nuclei is related to hydrolysis of high-energy phosphate bonds in nucleotide additives. The RNA is released predominantly in RNP: messenger-like RNA is released in RNP which have buoyant density and polypeptide composition similar to cytoplasmic messenger RNP, but which have distinctly different composition from those in heterogeneous nuclear RNP. Mature 18 and 28S ribosomal RNA is released in 40 and 60S RNP which represent mature ribosomal subunits. RNA transport proceeds with characteristics of an energy-requiring process, and proceeds independently of the presence or state of fluidity of nuclear membranes. The energy for transport appears to be utilized by a nucleoside triphosphatase (NTPase) which is distributed mainly within heterochromatin at the peripheral lamina. Photoaffinity labeling has identified the pertinent NTPase as a 46 kD polypeptide which is associated with nuclear envelope and matrix preparations. The NTPase does not appear to be modulated via direct phosphorylation or to reflect kinase-phosphatase activities. A large number of additives (including RNA and insulin) produce parallel effects upon RNA transport and nuclear envelope NTPase, strengthening the correlative relationship between these activities. Of particular interest has been the finding that carcinogens induce specific, long-lasting increases in nuclear envelope (and matrix) NTPase; this derangement may underlie the alterations in RNA transport associated with cancer and carcinogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nucleocytoplasmic RNA transport. 241 44

Enzyme-histochemical investigation of pancreatic carcinogenesis in male Wistar rats treated at the age of 19 days by a single dose of 30 mg azaserine/kg body wt led to the detection of a new 'marker' for the recognition of foci of atypical acinar cells: the Mg2+-dependent ATPase. The two well-known populations of pancreatic atypical acinar cell foci, classified histologically as basophilic and acidophilic foci, showed a decreased and strongly increased ATPase reaction, respectively. The enhanced enzyme activity of the acidophilic foci has been characterized as unspecific nucleoside polyphosphatase. To validate the new marker, comparative quantitative evaluation was performed on haematoxylin and eosin-stained paraffin sections and ATPase-stained cryostat sections of the same pancreata of 25 azaserine-treated rats. Evaluation of basophilic ATPase-deficient foci of small diameter was more reproducible in haematoxylin and eosin-stained sections, while small acidophilic strongly ATPase-positive foci could be detected more reliably by the ATPase staining technique. The number of foci/cm3 pancreas was similar for both staining techniques above a focus diameter of about 100 microns for basophilic foci and 200 micronfor acidophilic foci. There were more acidophilic than basophilic foci/cm3 pancreas, and the acidophilic foci had significantly larger mean focal diameters than the basophilic foci. Together with the strong acidophilic staining of the latter emerging adenoma, this suggests that the acidophilic foci represent a neoplastic cell population progressing eventually to pancreatic carcinoma. The new 'marker' enzyme ATPase may greatly facilitate further investigations into the role of these putative preneoplastic lesions in pancreatic carcinogenesis.
Carcinogenesis 1986 Mar
PMID:Adenosine triphosphatase, a new marker for the differentiation of putative precancerous foci induced in rat pancreas by azaserine. 241 8

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

Normal human bronchial epithelial cells were infected with SV40 virus or an adenovirus 12-SV40 hybrid virus, or transfected via strontium phosphate coprecipitation with plasmids containing the SV40 early region genes. Colonies of morphologically altered cells were isolated and cultured; these cells had extended culture lifespans compared to normal human bronchial epithelial cells. All cultures eventually underwent senescence, with the exception of one which appears to have unlimited proliferative potential. Colonies arising after viral infection were screened for virus production by cocultivation with Vero cells; only viral nonproducer cultures were analyzed further. The cells retained electron microscopic features of epithelial cells, and keratin and SV40 T-antigen were detected by indirect immunofluorescence. All of the cultures were aneuploid with karyotypic abnormalities characteristic of SV40-transformed cells. No tumors formed after s.c. injection of the cells in nude mice. These cells should be useful for studies of multistage bronchial epithelial carcinogenesis.
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PMID:Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes. 245 Jun 41

5-Azacytidine (5-aza-CR) and six of its analogs were examined for their ability to induce trifluorothymidine (TFT) and/or 6-thioguanine (6TG) resistance in L5178Y mouse lymphoma cells. These analogs were 5-aza-2'-deoxycytidine (5-aza-CdR), 5-fluoro-2'-deoxycytidine (5-FCdR), 5,6-dihydro-5-azacytidine (dH-aza-CR), 6-azacytidine (6-aza-CR), cytidine (CR) and 1-b-D-arabinofuranosylcytosine (ara-C). 5-Aza-CR and 6-aza-CR were examined for their ability to induce 6TG-resistant colonies and results demonstrated no effect. At least a 5-fold increase in TFT resistance was observed for 5-aza-CR, 5-aza-CdR, 5-FCdR, dH-aza-CR and ara-C. The concentration at which these compounds induced TFT resistance correlated well with the potential of the nucleoside analogs to induce differentiation in C3H10T1/2 cells as determined by Constantinides et al. (Nature, 267, 364-366, 1977). In L5178Y mouse lymphoma (MOLY) cells, 5-aza-CR induced TFT resistance and produced both small and large colonies. Previous studies using mammalian cells showed the absence of mutagenic activity with 5-aza-CR and some of its analogs at the ATPase and hgprt loci. However, the different spectrum of DNA lesions detected at the tk locus may be responsible for the response of MOLY cells to 5-aza-CR.
Carcinogenesis 1989 Nov
PMID:TFT and 6TG resistance of mouse lymphoma cells to analogs of azacytidine. 247 9

The ability of mutagens to transform benign papillomas to malignancy in the mouse skin model of multistage carcinogenesis [Hennings et al. Nature 303, 67-68 (1983)] suggests that multiple events may underlie carcinogenic progression, and that mutagenic exposures separated by time can act synergistically. Such synergism may result from initial mutagenic exposure which induces heritable sensitivity to subsequent mutagenic exposures. For example, progeny of X-irradiated V79 cells are hypersensitive to subsequent mutation induced by psoralen plus long-wave ultraviolet light, PUVA [Frank and Williams, Science 216, 307-308 (1982)]. In the present studies 100 to 200 surviving clones of short-wave ultraviolet light (UVC) irradiated V79 cells were assayed for mutation at two loci. Cultures derived from these cells were found to be hypermutable at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus following exposure to PUVA, but showed mutant frequencies similar to control cells following UVC challenge at the HGPRT and ATPase loci.
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PMID:Heritable hypersensitivity to induced mutagenesis in the progeny of cell populations exposed to UVC (254 nm). 252 33

Normal human melanocytes, which require the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) for growth in culture, were transfected with a SV40 T-antigen-containing plasmid by using the technique of electroporation, and were scored for colonies of morphologically altered cells. The frequency of transformed colonies was higher when selection was done in the absence rather than the presence of TPA in the medium. Three cell lines derived from transformed colonies were characterized. All show an enhanced growth rate compared to parental cells, anchorage independence, loss of dependence on medium supplements for growth, chromosomal abnormalities, an extended life span, and growth inhibition by TPA. They express nerve growth factor receptor and Mr 97,000 protein, melanotransferrin, two antigens usually associated with melanocytic cells, but the transformed cells are not pigmented. The three cell lines underwent crisis at about passage 10 posttransfection; one cell line recovered and appears to have unlimited growth potential. None of the cell lines is tumorigenic. They should be interesting models for studying multistage carcinogenesis in human cells and transcriptional activation by TPA.
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PMID:SV40-transfected human melanocyte sensitivity to growth inhibition by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. 254 1

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.
Carcinogenesis 1989 Oct
PMID:Comparison of three rat liver foci bioassays--incidence of preneoplastic foci initiated by diethylnitrosamine. 257 25


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