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)

Although most mammalian cell lines can utilize either nicotinic acid or nicotinamide for the biosynthesis of nicotinamide adenine dinucleotide (NAD), thymidine kinase-deficient, mouse 3T3-4F cells are unable to utilize nicotinic acid. When 3T3-4E cells were fused with human D98/AH2 cells, autoradiography showed that the resultant heterokaryons synthesized NAD from nicotinic acid at rates comparable to the human parental cell. The rate of nicotinic acid utilization in heterokaryons remained unchanged over the four-day period of study following cell fusion. In contrast to the results observed with heterokaryons, nicotinic acid utilization was markedly reduced in hybrid cells. Of 100 hybrid clones examined at four or five days following cell fusion, 60 utilized nicotinic acid at rates less than one tenth that of the parental human cell. Similar results were observed in hybrid clones at nine or ten days following fusion. Uniformly high rates of NAD biosynthesis were observed in hybrid clones with nicotinamide as the precursor. This excludes the possibility that the reduction in nicotinic acid utilization in hybrid cells is due to a general metabolic dysfunction. The biochemical mechanism by which nicotinic acid utilization is markedly reduced has not been determined with certainty, however, several observations suggest genetic suppression.
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PMID:Autoradiographic studies of nicotinic acid utilization in human-mouse heterokaryons and inhibition of utilization in newly-formed hybrid cells. 17 18

Mutations in the viral gene coding for the thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) induced by herpes simplex virus have been obtained by selection of virus resistant to bromodeoxyuridine when grown in thymidine-kinase-deficient LMTK- mouse cells. Proteins labeled after infection of Vero (monkey) cells with herpes simplex virus were analyzed by gel electrophoresis and one protein of about 40,000 daltons was consistently altered in a number of thymidine-kinase-deficient mutants. Many viral mutants lacked this peptide and one class of these mutants induced the synthesis of new shorter peptides. Revertant virus could be selected which simultaneously regained the ability to induce thymidine kinase activity, regained the intact thymidine kinase peptide, and lost the ability to synthesize the shorter peptide fragment. These mutants comprise a class of animal virus mutants which have the properties expected of peptide chain termination mutants.
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PMID:Possible peptide chain termination mutants in thymide kinase gene of a mammalian virus, herpes simplex virus. 17 94

Simultaneous infection of primary rabbit kidney cells with HSV type 1 TK+ and a TK- strain results in a mutual influence of both viruses on the induction of thymidine kinase (TK). TK+ virus has an enhancing and TK- virus a depressing effect on TK induction by a superinfecting TK+ virus. The enzyme induction depends on the ratio of multiplicities of both viruses. The mutual influence on TK induction depends further on the time of addition of the superinfecting virus: the effect of the second virus can still be observed when given 6 hours after primary infection. Identical phenomena can be observed using combinations with HSV type 2 or Pseudorabies viruses. The ability of HSV to induce TK is progressively inactivated with increasing the time of UV-irradiation. The depressing effect of a TK- strain and the stimulating effect of a TK+ strain on superinfecting TK+ strains is UV-sensitive: after 6 minutes of UV-irradiation neither inhibition nor stimulation of TK induction by a superinfecting TK+ strain can be observed. Infection by long-term (20 minutes) UV-irradiated TK+ strains results in a depression of TK induction by a superinfecting TK+ virus. Long-term irradiation of the TK- virus does not show this effect. Cytosine-arabinoside has no effect on the mutual influence of TK induction by TK+ and TK-strains; the phenomenon of mutual depression therefore has to be considered an early process.
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PMID:Influence of double infections on the induction of thymidine kinase by UV-irradiated herpes simplex virus types 1 and 2 and pseudorabies virus. 17 20

Deoxyribonucleoside triphosphate pools were analysed in both exponentially growing and serum starved wild type BHK C13 cells and in a derivative of this cell line which lacks both thymidine kinase and deoxycytidine kinase activities, before and after infection with herpes simplex virus. Serum starved BHK cells had low levels of all four deoxyribonucleoside triphosphates. In exponentially growing cells all pools were expanded, the pool of dCTP being largest and dGTP the smallest. The dATP and dTTP pools were of intermediate sizes. In exponentially growing deoxypyrimidine kinase free cells the pools, with respect to level and distribution, were the same as those observed in wild type cells. After infection with herpes simplex virus there were marked changes in the levels of all deoxyribonucleoside triphosphate pools; the most predominant being a 25- to 50-fold expansion of dTTP pool. The pools of dCTP and dGTP also increased while the pool of dATP was very much reduced. These effects could be observed in both wild type and mutant cells.
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PMID:Deoxyribonucleoside triphosphate pools in herpes simplex type 1 infected cells. 17 22

In tissue culture experiments, cells derived from glioma 26, a transplantable tumor of C57B1/6 mice, were sensitive to both floxuridine (5-fluorodeoxyuridine) and 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl)phosphate, an enzyme-mediated drug activated by 5'-nucleotide phosphodiesterase. When these compounds were tested on the tumor in animals at a level of 5 mg/kg for 5 days, tumor growth was inhibited approximately 20% by both compounds. When higher levels of 5-fluorodeoxyuridine, 100 mg/kg four times weekly throughout the lifespan of the mouse, were given, the tumor, although inhibited at first, developed resistance and continued to grow until it killed the animal. Phosphodiesterase levels in the tumor rose as the tumor grew. On the other hand, thymidine kinase levels dropped as anticipated from the known 5-fluorodeoxyuridine-resistant hepatoma tissue culture data. This enzyme pattern was maintained in transplantable mouse glioma lines established from the resistant tumors. One of these lines, tested at a level of 5 mg/kg for 5 days, showed no response to 5-fluorodeoxyuridine but was still sensitive to 5-fluorodeoxyuridine-5'-(5-iodo-3-indolyl) phosphate. These experiments, therefore, offer a model system and a rationale for the design and study of more compounds that could be activated by the enzyme phosphodiesterase. Such compounds might be used alternatively when resistance to 5-fluorodeoxyuridine develops, a common clinical experience in the use of this anticancer drug.
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PMID:5'-nucleotide phosphodiesterase activity of floxuridine-resistant mouse glioma. 17 49

Two linked human genes which code for the expression of cytosol thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) and galactokinase (ATP:D-galactose 1-phosphotransferase, EC 2.7.1.6) have been cotransferred via purified metaphase chromosomes from the human lymphoblastoid cell line WI-L2a, into mouse L-cells [B82 and LM(TK-)]. Both genes have previously been shown to be closely linked on the human chromosome E17, band q21-22. Coexpression of both human enzyme markers was detected in two out of eight gene transfer clones, whilst the remaining six clones contained only human cytosol thymidine kinase, as shown by electrophoretic techniques. A further 23 human enzyme markers corresponding to 15 different human chromosomes were found to be absent in these gene transfer clones. No human chromosome or chromosomal fragment could be detected by karyotype analyses. Some of the gene transfer clones rapidly lost the transferred donor material when grown in nonselective medium, whereas others expressed a stable phenotype under these conditions. Prolonged maintenance in selective medium favors the survival of gene transfer cells expressing a stable phenotype. Possibly these cells harbor the donor genes integrated into a recipient chromosome.
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PMID:Cotransfer of two linked human genes into cultured mouse cells. 17 84

A cytoplasmic form of thymidine kinase was detected in sera from rats bearing Morris hepatoma 7777. Polyacrylamide electrophoretic properties demonstrate similarity between the serum enzyme extracted from hepatoma tissue. This form of thymidine kinase has also been described in normal human fetal tissue and a variety of human tumor cells. The results suggest that serum isoenzymes of thymidine kinase may be a useful adjunctive test for the presence of certain types of malignant tumors.
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PMID:Tumor-associated thymidine kinase in the sera of rats with transplanted hepatomas. 17 42

After nitrous acid mutagenesis of herpes simplex virus type 1 (HSV-1), a mutant, 1093, was isolated which, during productive infection, induced very low levels of thymidine kinase (tk). The mutant virus was found, after UV irradiation, to be unable to transform L cells lacking tk (Ltk-) to a tk+ phenotype as chararcterized by growth of the cells in a modified HAT-selective medium containing 1.6 X 10(-5) M thymidine. Cells transformed by wild-type virus grew vigorously under the same conditions. The mutant was able to transform Ltk- cells if the medium contained 10(-3) M thymidine. These transformed cells maintained their conditional character and would not grow in low concentrations of thymidine in selective medium. Therefore, this mutant is conditional on the thymidine concentration in the selection medium in its ability to transform Ltk- cells to a tk+ phenotype. The conditionally transformed cells could be supertransformed with wild-type UV-irradiated HSV-1 to a phenotype which would grow in low-thymidine selective medium. The frequency of supertransformation closely approximated the frequency of transformation of Ltk- cells by wild-type virus. Supertransformation at high frequency could not be effected by mutant 1093 or the tk- mutant B2006. These results indicate that the presence of HSV-1 genetic information in HSV-1-transformed cells does not preclude the acquisition by these cells of at least one additional HSV-1 gene, that for tk.
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PMID:Mutant of herpes simplex virus type 1 conditionally able to transform thymidine kinaseless L cells to a tk+ phenotype. 17 26

The effect of dietary zinc levels on DNA synthesis in transplanted hepatomas induced by 3'-methyl-4-dimethyl-amino-azobenzene was investigated. DNA synthesis was found to be reduced (P less than 0,01) in rats maintained on diets low in zinc (0,5 mug/g) and high in zinc (less than 500 mug/g) when compared with the control animals given 60 mug zinc/g ration. Subsequently, the effect of dietary zinc intakes on the activity of 2 zinc-dependent enzymes associated with DNA synthesis--thymidine kinase and DNA polymerase--was studied. Both thymidine kinase and DNA polymerase activity was significantly reduced in animals receiving the zinc-deficient (0,5 mug/g) and zinc-supplemented (less than 500 mug/g) diets when compared with the control animals (60 mug/g). The data indicated that the DNA synthesis was the primary locus associated with zinc deficiency and zinc supplementation in proliferating tumour tissue, and that the site of action of zinc in this process was probably thymidine kinase, since there was considerable doubt concerning the role of DNA polymerase in DNA synthesis.
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PMID:A site of action for zinc in neoplastic tissue. 17 58

Transformation potential of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) was quantitatively compared in a system selecting for biochemical transformants. The highest frequency of transformation was obtained with HSV-2 strain 333. The transformation rates for two strains of HSV-1 were lower and distinctly different from HSV-2 and from each other. The dose of inactivating ultraviolet light received by the virus and the multiplicity of infection proved to be critical components of the procedure. Clones of these biochemically transformed cells expressed HSV-specific antigens, altered cell morphology, and increased levels of thymidine kinase activity. Isolates of HSV-1 recovered from the same site 11 years apart yielded similar transforming frequencies. These results suggest that this assay should prove useful in further characterizing the biological properties of HSV.
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PMID:Comparison of herpes simplex virus isolates using a quantitative selection assay for transformation. 17 66


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