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)

Cadmium administered shortly before or after partial hepatectomy blocks in a dose-dependent manner the increase of thymidine and thymidylate kinase activities in regenerating rat livers. The effect of cadmium can be partially antagonized by simultaneous zinc administration. The intraperitoneal injection of cadmium is more effective than its subcutaneous administration. While there are in vitro differences in the sensitivity of thymidine kinase and thymidylate kinase towards Cd2+-, Zn2%- and Cu2+-ions, both enzymes are equally depressed following their in vivo administration. Cadmium displays the highest inhibitory activity and resembles in this respect beryllium [1].
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PMID:Metabolic alterations of liver regeneration. XV. Cadmium-mediated depression of thymidine and thymidylate kinase induction in rats. 22 69

In rats, of the Wistar-Porton strain, a single intravenous injection of 1.25 mg Cd2+ between days 9 and 15 of gestation results in a high incidence (80% of hydrocephalus, together with other malformations in the fetuses, examined on day 20. This dose is critical, since 1.1 mg Cd2+/kg is not teratogenic, while 1.35 mg Cd2+/kg kills all the embryos. Intravenous injection of Cd2+ to the pregnant rat on day 12 causes a dose-dependent inhibition of placental Zn2+ transport. At the teratogenic dose, Zn2+ transport is inhibited by about 75% at 4 hr. Thereafter, inhibition decreases with time but is still significant at 48 hr. At 20 hr after administration of Cd2+ the embryonic concentration of Zn2+ is depressed by 33%. In the whole embryo the activity of the Zn2+-dependent thymidine kinase is inhibited by about 60% at 4 hr and at 20 hr the DNA concentration is reduced significantly. Placental transport of 14C-leucine and 14C-uridine, as well as the embryonic incorporation of these precursors into protein and RNA is unaffected at least at short times after the administration of Cd2+. It is possible therefore, that the teratogenic effects of Cd2+ may be related to the inhibition of DNA synthesis in the embryo.
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PMID:Acute effects of cadmium on the pregnant rat and embryo-fetal development. 48 38

A serum-dependent and two serum-independent variants of the Bowes melanoma cell line, RPMI7272, were transfected with plasmids containing a geneticin-resistance (neo) gene transcribed by the HSV thymidine kinase promoter and an SV40 T antigen gene under control of the mouse metallothionein I promoter. T-antigen increased the cloning efficiency of the serum-dependent cell line in soft-agar more than 50-fold, but cloning efficiency of serum-independent lines was not increased. Trypsinization of serum-independent lines required 100 times lower concentrations of trypsin than serum-dependent cells. Human metal-inducible T-antigen-producing (HMT) melanoma cells supported replication of transfected plasmids containing an SV40 origin of replication. Transient expression of interferon or plasminogen activator from such plasmids was 40-fold higher than in untransformed melanoma cells and could be enhanced 30-fold more by stimulation of transcription of the T antigen gene with cadmium chloride. HMT cells can be grown in suspension and thus may represent an attractive alternative to monkey kidney COS cells.
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PMID:Transformation of Bowes melanoma cells with SV40 T antigen. 136 20

Earlier results suggested that the functional hemizygosity of genes in pseudodiploid Chinese hamster ovary (CHO) cells is due to the silencing of one allele by DNA methylation. From this one could make a strong prediction that we have now been able to confirm by genetic experiments, using thymidine kinase (TK) alleles. TK- mutants induced by ethylmethane sulphonate (EMS) were all revertible to TK+ at high frequency by the demethylating agent 5-azacytidine (5-aza-CR). This revertibility was due to reactivation of a silent nonmutant TK allele. Further mutagenesis by EMS yielded TK- derivatives that were no longer revertible by 5-aza-CR; these are assumed to have mutations in both alleles. TK- cells were also transfected with equine herpes virus TK+ DNA, and the TK+ derivatives were shown to be markedly less stable than cells with the normal TK+ gene. CHO cells lack metallothionein activity (sensitive to cadmium), and also require proline for growth, because genes have become silenced during the establishment of the cell line. In both cases 5-aza-CR reactivates these genes to give the cadmium resistant and proline independent phenotypes. Long-term experiments with reactivants in the absence of selection showed that the genes become silent, presumably as a result of de novo methylation. A strain resistant to cytosine arabinoside (araCR) was also resistant to 5-azadeoxycytidine (5-aza-CdR), but not to 5-aza-CR, which would be expected if the araCR strain lacked deoxycytidine kinase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for allelic exclusion in Chinese hamster ovary cells. 170 54

The bacterial xanthine-guanine phosphoribosyltransferase (GPT) gene was fused to a metal-responsive promoter and transfected into a murine cell line. Clonal transformants harboring metal-responsive or nonresponsive GPT genes (using a thymidine kinase promoter) were then studied for the loss of transfected gene function either during periods of constitutive expression or during periods of induced activity. Nontoxic levels of cadmium and zinc markedly reduced the frequency of mutagenesis in all transfected lines irrespective of transcriptional status. A survey of 17 GPT-clones derived from two original transfectants showed partial or complete excisions of the transfected gene in every case. These studies show that quantities of cadmium and zinc that induce metallothioneins also suppress the incidence of deletions in murine cells.
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PMID:Deletion of stably integrated DNA is suppressed by cadmium and zinc. 259 74

We describe a human genomic clone containing the metallothionein (MT) IF and MT IG genes. Southern blot analysis and partial DNA sequence determinations show that these genes are organized in a head-to-head fashion and are located approximately 7.0 kilobases apart from each other. Sequence analysis shows that the MT IF gene contains three exons separated by two introns. All of the intron-exon junctions are defined by the GT-AG rule. The 5' flanking region shows the presence of a duplicated metal regulatory element (TGCGC CCGGCCC) important in heavy-metal induction of this gene and a sequence for its basal level expression (GCGGGGCGGGTGCAAAG). The 5' flanking region is also highly G + C rich (approximately 75%) and contains several GC boxes (GGGCGG), probably important in the binding of transcription factors. The TATAA box and the AATAAA sequence are represented by their variants, the TATCAA box and the AATTAA sequence, respectively. This gene is functional and inducible by heavy metals but not by dexamethasone in mouse LMTK- cells after its transfer on a plasmid containing the herpes simplex virus thymidine kinase gene. Further studies on various human cell lines show that this gene is not expressed in a splenic lymphoblastoid cell line (WI-L2) but is expressed in two hepatoma cell lines (Hep 3B2 and Hep G2) in response to cadmium, zinc, and copper. Dexamethasone appears to have no significant effect on its expression. The studies suggest that the MT IF gene shows cell-type-specific expression and is differentially regulated by heavy metals and glucocorticoids.
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PMID:Structure, organization, and regulation of human metallothionein IF gene: differential and cell-type-specific expression in response to heavy metals and glucocorticoids. 302 27

A mouse cell line (Ltk-aprt-) which is resistant to the anti-viral effects of interferon also has a reduced ability to synthesize metallothionein on exposure to cadmium. Like the ability to respond to interferon, cadmium-induced metallothionein synthesis is restored to wild-type levels in clones obtained by introducing a thymidine kinase gene into Ltk-aprt-cells. Transfection of other genes does not have such an effect. Since metallothionein expression is also activated by interferon the results suggest that the regulation of several genes which are responsive to interferon can be modulated by specific sequences present in the Herpes virus thymidine kinase gene.
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PMID:Activation of metallothionein expression is potentiated by DNA sequences present in the herpes simplex virus thymidine kinase gene. 303 84

Cloned fragments of DNA including the Drosophila melanogaster metallothionein gene Mtn and different amounts of 5' flanking sequences were introduced into flies by P-element-mediated germ line transformation. Comparison of RNA levels in different transformants revealed that metal-regulated and tissue-specific expression of Mtn requires no more than 373 base pairs upstream of the initiation site of transcription. Transformants having an additional, transcribed copy of Mtn could tolerate increased concentrations of cadmium, indicating that Mtn expression is directly related to this phenotype. In separate experiments, these D. melanogaster promoter sequences were fused to the coding sequences of the herpes simplex virus thymidine kinase (TK) gene. After transfection of this fusion into baby hamster kidney cells, increases in TK activity and accumulation of TK RNA were inducible by metals. A series of 5' and 3' deletions showed that D. melanogaster sequences from -130 to -6 were sufficient to confer metal-regulated expression to the TK gene. The function of the D. melanogaster metallothionein promoter in mammalian cells indicates that the mechanism controlling metal regulation is evolutionarily conserved.
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PMID:A DNA segment controlling metal-regulated expression of the Drosophila melanogaster metallothionein gene Mtn. 311 May 97

The mutagenic effect of cadmium chloride on somatic cells of F1 hybrid mice CBA X C57B1/6J in vivo and on an established line of CHO-ATZ-2 Chinese hamster cells in vitro has been studied. The induction of micronuclei has been demonstrated in mouse marrow cells as well as induction of point mutations at loci controlling the synthesis of hypoxanthine-phosphoribosyltransferase, thymidine kinase, adenine phosphoribosyltransferase and the resistance of Na+/K+ ATPase to ouabain in the cell line CHO-AT-2. A peak of mutagenic activity under the action of subtoxic doses of cadmium chloride has been revealed.
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PMID:[Mutagenic action of cadmium chloride in mammals]. 343 31

Mercuric mercury (Hg2+), like cadmium (Cd2+), interferes with the transport of certain essential metals to the conceptus in the pregnant Wistar rat and, at 48 h after the IV injection of a teratogenic dose (0.79 mg Hg2+/kg body weight) on day 12 of gestation, the foetal concentrations of Zn2+, Cu2+ and Fe3+, but not of Mg2+, are reduced significantly. Both Hg2+ and Cd2+, at teratogenic dose levels, inhibit the placental and foetal uptake of 65Zn2+ and 67Cu2+, but possibly by different mechanisms. In addition, the effects of Hg2+, at different times after dosing, on the uptake of these labelled tracers and of 59Fe3+, administered as 15-min pulses, do not parallel the changes in the placental and foetal concentrations and contents of the endogenous, stable metallic ions. The teratogenic dose of Hg2+ inhibits the placental and foetal uptake of L-[4,5-3H]-leucine, but not the incorporation of the labelled amino acid into foetal protein. In contrast, the corresponding dose of Cd2+ inhibits both leucine uptake and protein synthesis in the placenta and foetus. Similarly, Cd2+ inhibits the uptake of [2-14C]-thymidine and its incorporation into foetal DNA, whereas Hg2+ reduces the placental and foetal uptake, but has little or no effect on the utilization of the nucleoside. Since both Cd2+ and Hg2+ reduce the foetal uptake of 65Zn and the foetal concentration of Zn, but only Cd2+ interferes with DNA synthesis, it is unlikely that the inhibition of the metabolism of thymidine can be attributed to reduction in thymidine kinase activity in consequence of foetal Zn deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of some biochemical effects of teratogenic doses of mercuric mercury and cadmium in the pregnant rat. 371 28


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