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

Infection of Vero cells with herpes simplex virus (HSV) causes a marked increase in the dTTP pool size of infected cells. In this study we examined the relative importance of the HSV-encoded ribonucleotide reductase (RR) and thymidine kinase (TK) in the increase of dTTP. In cells infected with an RR deletion mutant of HSV-1 strain KOS, there was no significant increase in the size of the dTTP pool, whereas the dTTP pool in HSV-1(TK-)-infected cells was increased in size to almost the same extent as that in HSV-1(TK+)-infected cells. Moreover, it was found that the increase in dTTP pool size was strongly inhibited by the addition of hydroxyurea, a specific inhibitor of RR, and 5-fluoro-2'-deoxyuridine, a specific inhibitor of thymidylate synthetase. These results suggest that the induction of viral RR is of primary importance in the increase of dTTP pool size in HSV-1-infected Vero cells.
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PMID:Role of viral ribonucleotide reductase in the increase of dTTP pool size in herpes simplex virus-infected Vero cells. 164 84

Thymidylate synthase and thymidine kinase, which catalyze the formation of thymidylate via the de novo and salvage pathways, respectively, are rate-determining enzymes in DNA synthesis. The increases in the activities of hepatic thymidylate synthase and thymidine kinase were significantly suppressed at 24 h after 70% partial hepatectomy in rats that had been administered cycloheximide. Concomitantly, other regenerative parameters such as the liver weight and contents of protein, RNA, and DNA were also significantly reduced in 24-h regenerating liver of cycloheximide-treated rats. When actinomycin D was injected, the activity of thymidine kinase, the liver weight, and contents of protein, RNA, and DNA were completely depressed in 24-h regenerating liver. However, the activity of thymidylate synthase in actinomycin D-administered rats rose to the level similar to the control (70% partially hepatectomized). The immunoblotting assay showed that thymidylate synthase is newly synthesized during liver regeneration after partial hepatectomy without being affected with actinomycin D.
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PMID:Effect of cycloheximide and actinomycin D on thymidylate synthase and thymidine kinase in regenerating rat liver after partial hepatectomy. 170 95

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). The administration of 3'-MeDAB in combination with 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil (UFT) delayed the appearance of oval cells and the formation of hyperplastic nodules, which were observed in the liver from 3 and 5 weeks, respectively, after the onset of 3'-MeDAB feeding, and also delayed the transient increase of serum alpha-fetoprotein level, which transiently peaked at 5 weeks, and completely suppressed the transient increase of tissue thymidylate synthetase activity, but not thymidine kinase, which were induced by 3'-MeDAB at 5 weeks, and finally reduced markedly the incidence of hepatocarcinomas. These results indicate that the suppression of de novo synthesis in pyrimidine metabolism prevents hepatocarcinogenesis.
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PMID:Inhibition by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats. 171 76

An avian thymidine kinase deficient (TK-) fibroblast cell line (QTTK-) was established from a Japanese quail cell line, QT35, and characterized the biological properties. QTTK- could grow in the presence of 5-bromo-2'-deoxyuridine (BUdR, 100 micrograms/ml) and not in the growth medium with hypoxanthine-aminopterin-thymidine. Compared to QT35 cells, the 3H-thymidine incorporation of the QTTK- cells and the TK activity of the cell extract significantly decreased to 0.3% and 0.5%, respectively. In the thymidylate synthetase activity, the karyotype, and the sensitivities to either fowlpox virus (FPV) or herpesvirus of turkeys (HVT), OTTK- cells were similar to the parental QT35 cells. Since QTTK- cells were permissive to FPV and HVT infections and these viruses could not grow in the presence of 50 to 75 micrograms/ml of BUdR, QTTK- cells may be useful for the construction of recombinant FPV and HVT that have foreign genes within the TK gene of the virus genome.
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PMID:Establishment and characterization of a thymidine kinase deficient avian fibroblast cell line derived from a Japanese quail cell line, QT35. 183 32

A polymerase chain reaction system for the detection of varicella-zoster virus was established. Of 25 nucleotides, 4 oligonucleotide pairs (regions of thymidine kinase, thymidylate synthetase, glycoprotein I, and immediate early gene) were synthesized. The first three oligonucleotide pairs could be used as primers on the basis of specific DNA amplification. Varicella-zoster virus DNA was amplified by this polymerase chain reaction system in 20 of 20 vesicle samples, 5 of 6 crusts, and 12 of 13 throat swabs collected from patients with clinical varicella.
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PMID:Detection of varicella-zoster virus (VZV) DNA in clinical samples from patients with VZV by the polymerase chain reaction. 838 18

The relationship between chromosome anomalies and metabolic modifications in human colorectal cancers grafted into nude mice was studied. Two distinct chromosomal patterns have been demonstrated i.e., monosomic type (MT) characterized by multiple chromosome losses or deletions always involving chromosome 18, and trisomic type (TT) characterized by progressive gains of chromosomes. Grafted tumors conserve original karyotypes observed on corresponding primary tumors. Most changes involve the loss of chromosomes carrying genes encoding for enzymes of the de novo pathways and the gain of chromosomes carrying genes encoding for enzymes of the salvage pathways of nucleotide synthesis. In MT tumors the long arm (q) of chromosome 17 is frequently duplicated in association with a deletion of the short arm, forming an isochromosome 17q. The activities of 3 enzymes, thymidylate synthetase (TS) mapped on chromosome 18, thymidine kinase (TK) and galactokinase (GalK), both mapped on chromosome 17q, were studied. TS is a de novo enzyme and TK and GalK are salvage enzymes. A clear correlation could be demonstrated between tumor types and enzyme activities: MT tumors had lower TS and higher TK and GalK activities than TT tumors. These differences were too large to result from a gene dosage effect only. These data suggest that serial studies on grafted colorectal cancers give a better representation of metabolic disturbances than studies on fresh tumor samples, usually contaminated by non-cancerous cells.
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PMID:Activity of thymidylate synthetase, thymidine kinase and galactokinase in primary and xenografted human colorectal cancers in relation to their chromosomal patterns. 200 48

Thymidine auxotrophs (B3T) of rat nerve-like cells (B103) were isolated. B103 cells were preincubated in a thymidine medium and mutagenized with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Afterward, cells were incubated in a medium supplemented with dialyzed fetal calf serum and then treated with 5-fluorodeoxyuridine for 24 h. Next, cells were grown in a thymidine medium for twenty days. Thymidine auxothrophs were thus obtained and one clone of them was designated B3T cells. The modal number of chromosomes in B3T cells was 85. Growth tests revealed the following interesting facts: (1) The medium containing pyrazofurin and uridine could not support the growth of B3T cells, but the addition of thymidine to such a medium enabled cells to grow. (2) Even deoxyuridine supported the growth of B3T cells when added to the medium of pyrazofurin and uridine. These findings suggest that the catalytic ability of thymidylate synthetase in B3T cells may have decreased, probably due to the decreased affinity of the enzyme molecules to the substrate (dUMP), and that thymidine kinase activity was high enough to support the growth of B3T cells. B3T cells have maintained the ability to differentiate and extend neurites in response to dibutyryl-cyclic AMP as also demonstrated in wild cells (B103). B3T cells will be available for genetical and molecular biological studies of neuronal cells.
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PMID:Isolation of thymidine-requiring variants from rat nerve-like cells. 216 41

The increases in the activity of hepatic thymidylate synthetase and thymidine kinase, which catalyzes the formation of thymidylate via the de novo and salvage pathways, respectively, were significantly suppressed 24 h after 70% partial hepatectomy in female rats administered either alpha- or beta-adrenoreceptor antagonists. The injection of beta-antagonist to male or ovariectomized female rats had no effect on the activities of these enzymes. Only alpha-adrenoceptor antagonist depressed these enzymatic activities of 24-h-regenerating liver in male and ovariectomized female rats. The decrease of the activities of thymidylate synthetase and thymidine kinase was accompanied by a concomitant reduction of DNA content in 24-h-regenerating liver. It is concluded that catecholamine regulates the female rat liver regeneration through both alpha- and beta-adrenergic pathways by the inductions of thymidylate synthase and thymidine kinase, while in adult male and ovariectomized female rats, only the alpha-mediated pathway is involved.
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PMID:The sex difference in the regulation of liver regeneration after partial hepatectomy in the rat. 231 4

The controversial issue of the effects of prednisolone and 17 beta-estradiol on replication of fetal rat pancreatic islets in culture was studied using 32P and [3H]thymidine as probes for studying DNA synthesis. DNA synthesis was not affected by the steroid hormones, as was evident from the rate of incorporation of 32P into total DNA. Decreased incorporation of [3H]thymidine into DNA found in islets treated with either of these steroids seemed to reflect an inhibitory effect of these hormones on thymidine kinase, leading to decreased phosphorylation of labeled thymidine. In addition, the hormones stimulated the activity of thymidylate synthetase, thus enhancing the endogenous synthesis of thymidine and thereby diluting the specific activity of the [3H]thymidine added to the cultured islets. Further support for a lack of inhibition of growth of islet cells treated with steroid hormones was provided by the observation that prednisolone increased uridine kinase activity and RNA biosynthesis, both of which may participate in the growth of cells preceding mitosis and (the latter) in protein hormone biosynthesis.
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PMID:Regulation of pancreatic islet cell replication: an inquiry into the controversy regarding the effects of steroid hormones. 243 Jul 83

Various established antiherpetic drugs, including 1-beta-D-arabinofuranosylthymine (araT), acyclovir (ACV), 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), and structurally related analogues thereof, i.e. (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC), (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), and the carbocyclic analogues of BVDU (C-BVDU), IVDU (C-IVDU) and BVDC (C-BVDC), were evaluated for their inhibitory effects on the growth of murine mammary carcinoma (FM3A/0), murine leukemia (L1210/0) and murine fibroblast (LM/0) cells and the thymidine kinase-deficient (TK-) sublines derived from the FM3A/0, L1210/0 and LM/0 cells. BVDU, IVDU and BVDC showed a markedly increased cytostatic activity against the TK- cell lines. To determine the biochemical mechanism of the increased cytostatic action of these compounds toward TK- cell lines, BVDU and IVDU were further evaluated for their inhibitory effects on pyrimidine nucleotide metabolism, in particular thymidylate synthetase activity, their incorporation into DNA and into trichloroacetic acid (TCA)-insoluble material, and their effects on DNA, RNA and protein synthesis in both TK+ and TK- cells. No marked differences were noted in the interaction of BVDU and IVDU with these potential targets between TK+ and TK- cell lines. Furthermore, neither FM3A/0 nor FM3A/TK- cells expressed a significant phosphorylating activity for (125I) IVDU. However, BVDU and IVDU specifically inhibited the incorporation of (1-14C) mannose and (1-14C) glucose into glycoproteins of FM3A/TK- and L1210/TK- cells. To what extent the inhibition of the incorporation of these monosaccharides into glycoproteins may contribute to the increased cytostatic effects of BVDU and IVDU on TK- cells remains to be determined.
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PMID:Increased sensitivity of thymidine kinase-deficient (TK-) tumor cell lines to the cell growth inhibitory effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and related compounds. 243 29


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