Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Considerable thymidine kinase and pyrroline-5-carboxylate reductase activities were found in the plasma of rats bearing a transplanted lymphoma; neither activity was detected in plasma of hosts carrying hepatic, renal, mammary, or submaxillary gland tumors. All host livers exhibited signs of biochemical immaturity as indicated by the appropriate increases or decreases in the concentrations of the nine enzymes measured. The extent and time schedule of the changes in host liver varied with the enzyme and with the tumor that caused them. The hepatic concentrations of ornithine aminotransferase, arginase, pyrroline-5-carboxylate reductase, and glucokinase (all diminished), and of peptidyl proline hydroxylase and hexokinase (increased) were sensitive indicators of tumor growth in general. The concentration of ornithine aminotransferase decreased before the tumors became palpable. At more advanced stages, the high hepatic thymidine kinase activity distinguished the presence of hepatoma and lymphoma from those of all other equally fast-growing tumors. However, only in lymphoma-bearing rats did a fivefold elevation of hepatic thymidine kinase occur as early as 4 days after implantation. Additional observations on the lymphoma itself, on blood cells, and on the involuting thymus of normal rats indicate that the striking systemic effects of this tumor cannot be explained by a release of enzymes from the thymus or by the increased number of lymphoma cells present in blood or liver.
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PMID:The effect of lymphoma and other neoplasms on hepatic and plasma enzymes of the host rat. 18 34

The antibiotic distamycin A displays no inhibition of protein synthesis in HeLa cell cultures. In HSV infected HeLa cell monolayers the drug exerts a partial inhibition of virus induced thymidine kinase synthesis but is devoid of inhibitory effect on the increase of activity of DNA polymerase and on total DNA synthesis. The antiviral activity of distamycin A is based on a mechanism which appears to be different from that displayed by other drugs such as actinomycin and IUD.
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PMID:The effect of distamycin A on some biochemical functions of tissue cultures infected with Herpes simplex virus. 18 85

Phosphonoacetic acid (PAA) inhibited the synthesis of herpes simplex virus DNA in infected cells and the activity of the virus-specific DNA polymerase in vitro. In the presence of concentrations of PAA sufficient to prevent virus growth and virus DNA synthesis, normal amounts of early virus proteins (alpha- and beta-groups) were made, but late virus proteins (gamma-group) were reduced to less than 15% of amounts made in untreated infected cells. This residual PAA-insensitive synthesis of gamma-polypeptides occurred early in the virus growth cycle when rates were identical in PAA-treated and untreated infected cells. Passage of virus in the presence of PAA resulted in selection of mutants resistant to the drug. Stable clones of mutant viruses with a range of drug sensitivities were isolated and the emergence of variants resistant to high concentrations of PAA involved the sequential selection of mutants progressively better adapted to growth in the presence of the drug. Increased drug resistance of virus yield or plaque formation was correlated with increased resistance of virus DNA synthesis, gamma-protein synthesis, and resistance of the virus DNA polymerase reaction in vitro to the inhibitory effects of the drug. PAA-resistant strains of herpes simplex virus type 1 (HSV-1) complemented the growth of sensitive strains of homologous and heterologous types in mixed infections in the presence of the drug. Complementation was markedly dependent upon the proportions of the resistant and sensitive partners participating in the mixed infection. Intratypic (HSV-1A X HSV-1B) recombination of the PAA resistance marker(s), Pr, occurred at high frequency relative to plaque morphology (syn) and bromodeoxyuridine resistance (Br, thymidine kinase-negative phenotype) markers, with the most likely order being syn-Br-Pr. Recombinant viruses were as resistant or sensitive to PAA as the parental viruses, and viruses recombinant for their PAA resistance phenotype were also recombinant for the PAA resistance character of the virus DNA polymerase. The results provide additional evidence that the herpesvirus DNA polymerase is the site of action of PAA and illustrate the potential usefulness of PAA-resistant mutants in genetic studies of herpesviruses.
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PMID:Herpes simplex virus resistance and sensitivity to phosphonoacetic acid. 18 89

GM54VA human cells transformed by simian virus 40 (SV40) were fused with peritoneal macrophages obtained from three different mouse strains. All 27 hybrid clones studied were positive for SV40 tumor antigen in 100% of their cells and contained human chromosome 17. Human chromosome 17 was the only human chromosome present in five of the hybrid clones. Fusion of GM54VA cells and either thymidine kinase (EC 2.7.1.75)-deficient mouse or Chinese hamster fibroblasts resulted in the growth in hypoxanthine-aminopterin-thymidine medium of hybrid clones positive and negative for SV40 tumor antigen. Counterselection of the hybrid clones positive for tumor antigen in medium containing 5-bromodeoxyuridine resulted in the growth of hybrid cells that were negative for tumor antigen. These experiments indicate that negative for tumor antigen. These experiments indicate that SV40 is integrated in only one of the two parental human chromosomes 17. Because the genome of SV40 has been assigned to human chromosome 7 in two other SV40-transformed human cell lines, at least two different integration sites for SV40 would seem to be present in human cells: one located in human chromosome 7 and the other located in human chromosome 17.
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PMID:Assignment of the integration site for simian virus 40 to chromosome 17 in GM54VA, a human cell line transformed by simian virus 40. 18 10

The concentrations of 16 to 21 enzymes, representing various metabolic pathways, have been determined in human adult, fetal, and neoplastic lung. At midgestation, 12 enzymes (among them, several that metabolize amino acids) were above their adult values while 3 other enzymes were still at low concentrations. These signs of biochemical immaturity are contrasted and compared with those in fetal human liver and rat lung. The enzymic composition of the 11 human pulmonary tumors studied resembled that of the normal fetal lungs closely; the same 12 enzymes were elevated and the same 2 were decreased (compared to nonneoplastic adult lung) in both. The characteristic abnormality in the overall pattern of enzymes, in the concentrations of individual ones, and in the quality of pyrroline-5-carboxylate reductase was clearly evident in both primary and metastatic tumors. The mean concentrations of 10 enzymes in the tumors were significantly different (higher or lower) from those in the control lungs (p less than 0.001 to less than 0.05). The best markers of neoplasticity were thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, hexokinase, and pyrroline-5-carboxylate reductase. The results demonstrate that quantification of a small battery of enzymes, none of them tissue specific, can distinguish adult human lung from its neoplasms.
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PMID:The undifferentiated enzymic composition of human fetal lung and pulmonary tumors. 18 17

LTK-cells infected with UV-irradiated HSV produce transformants that contain a thymidine kinase (TK) activity not found in the parental LTK-line (Munyon et al., 1971). One of these (TK+) transformants (clone 139) has been analysed for the presence of the HSV genome. Reassociation kinetics studies with iodinated HSV DNA of specific activity of about 9 x 107 cpm/mug have established that there are approximately six copies of a fragment comprising about 15% of the HSV genome in HSV-transformed clone 139. Neither the parental LTK-nor a "revertant" cell line (clone 139 BUDR) obtained from clone 139 showed any detectable HSV-specific sequences. Analysis of data on RNA-125I-HSV DNA reassociation kinetics indicates that perhaps 5% of the HSV genome is transcribed in HSV-transformed clone 139. These results indicate that transformation is probably maintained by the presence of only a fraction of the HSV genome in the TK+ clones.
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PMID:Presence of a herpes simplex virus type 1 genome fragment in HSV-transformed cells. 19 Jan 47

N1-S1/FdUrd Novikoff hepatoma cells, which lack thymidine kinase activity, are resistant to 5-fluorouracil (FUra) as well as 5-fluorodeoxyuridine (FdUrd), suggesting that the pathway, FUra leads to FdUrd leads to FdUMP, is utilized for the conversion of FUra to FdUMP. However, the inhibition of thymidylate synthetase activity, the presumed target of FdUMP, by 1 X 10(-4) M FUra in intact N1-S1 Novikoff hepatoma cells, which have significant levels of thymidine kinase activity, is completely eliminated by 5 X 10(-4) M hydroxyurea, which is a potent inhibitor of ribonucleotide reductase. These results imply that the formation of ribonucleotides and does not involve thymidine kinase. This apparent dichotomy can be explained by the fact that, in addition to the well known lack of thymidine kinase activity, [14C]FUra conversion to ribonucleotides is greatly depressed in the N1-S1/FdUrd cells. Hence, the formation of FdUMP from FUra in Novikoff hepatoma cells apparently proceeds primarily via the intermediate formation of ribonucleotides. The decreased conversion of FUra to ribonucleotides in N1-S1/FdUrd cells decreases not only the ability of the analog to inhibit DNA synthesis, but also its effect on RNA metabolism. FUra, at a concentration of 1 X 10(-5) M, inhibits rRNA maturation in N1-S1 cells, but not in N1-S1/FdUrd cells. Since N1-S1/FdUrd cells are completely resistant to 1 X 10(-5) M FUra, whereas N1-S1 cells are completely inhibited by 1 X 10(-5) M FUra, even in the presence of 1 X 10(-4) M thymidine, the effects of FUra on RNA metabolism appear to contribute significantly to the cytotoxicity of the analog at higher drug concentrations.
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PMID:Metabolism of 5-fluorouracil in sensitive and resistant Novikoff hepatoma cells. 19 Feb 17

In arginine-deprived cells infected with simian virus 40 (SV40), both viral DNA and viral structural proteins were synthesized but infectious virus was not produced. The syntheses of cellular DNA, thymidine kinase and DNA polymerase were induced in virus-infected cells deprived of arginine but the maximum rate of synthesis of these enzymes occurred much later than that in infected cells incubated in the presence of arginine.
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PMID:The effect of arginine deprivation on DNA, thymidine kinase and RNA polymerase synthesis in simian virus 40-infected monkey kidney cells. 19 79

Fractions of heavy and light mitochondria are isolated from homogenates of homologous rat tissues (intact liver, regenerating liver within 24 hours after hepatectomy and 27 hepatoma) by means of differential centrifugation. It is found that tumour mitochondria have higher heterogeneity and lower buyoant density than mitochondria from normal hepatocytes. The activity of two enzymes of DNA precursors synthesis (ribonucleotide reductase and thymidine kinase) in subcellular fractions is demonstrated to correlate with the tissue growth rate. A single injection of cyclic AMP into hepatectomised rats resulted in the retardation of the regeneration process, and the activity of both enzymes reached its normal level in all the fractions studied after 24 hours after the operation. Thymidine kinase and ribonucleotide reductase are located mainly in the mitochondrial matrix, however, pronounced enzyme activity is observed also in membrane fractions. The activity of the enzymes in the fraction of external mitochondria membranes in rapidly growing tissues is 2--3 times as high as in the same fraction from normal rat liver.
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PMID:[Mitochondrial thymidine kinase and ribonucleotide reductase from rat liver and rat hepatoma 27]. 19 36

Increase of dThd-uptake 4 to 12 h after infection of BHK or primary rabbit kidney cells with Herpesvirus hominis of type 1 or 2 can be considered as an early function of the virus genome, because the presence of Cyd-Ara does not prevent the increase of uptake. However, increase of uptake can be prevented by addition of actinomycin D and cycloheximide early in the synthetic cycle. Two modes of uptake have been differentiated by kinetic analysis: at low substrate concentration dThd is taken up by 'facilitated transport', whereas at high substrate concentration (above 2-5 micronM) simple diffusion takes place. The Km of transport of normal BHK or primary rabbit kidney cells (1-4 or 0-5 micronM respectively) is not changed after infection. Only the Vmax increases from 8 to 26-6 pmol in BHK cells or from 2-9 to 9-0 pmol in primary rabbit kidney cells. This indicates that 'carrier sites' with identical affinity for dThd-transport are responsible for the increase of transport after infection. This increase of transport is correlated with the induction of a virus coded thymidine kinase (TK) and not with different types of c.p.e. or cellular damage. Transport of BdUrd increases in a similar manner to that of dThd after infection; transport of dCyd or dUrd increases only slightly, whereas the mechanism of dAdo or Urd uptake by infected cells is quite different.
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PMID:Thymidine transport in herpesvirus hominis type 1 and 2 infected BHK 21 cells. 19 42


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