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)

A transient rise in cyclic guanosine 3' : 5' monophosphate (c-GMP) in the liver was observed in rats in vivo 10--20 min after partial hepatectomy. A similar increase in c-GMP in the liver was also found in rats in vivo 15 min after infusion of TGH solution (a mixture of triiodothyronine, glucagon, and heparin). In both cases, inductions of ornithine decarboxylase [EC 4.1.1.17] and tyrosine aminotransferase [EC 2.6.1.5] were found 4 hr after the beginning of the experiments. Later, 22 hr after the surgical intervention or hormone infusion, thymidine kinase [EC 2.7.1.21] was activated and liver slices were able to incorporate [3H]thymidine into DNA. These biochemical phenomena were observed commonly in regenerating liver as well as in the liver of rats infused with TGH solution. c-GMP, but not c-AMP, could induce ornithine decarboxylase and tyrosine aminotransferase in isolated, perfused liver.
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PMID:Involvement of cyclic GMP in the initial stage of hepatocytes proliferation. 1 43

Reuber (H35) hepatoma cells were grown in medium containing 10(-5)M bromodeoxyuridine (BrdU), which was incorporated into their DNA. Cell growth rate was unaffected by BrdU for the first two generations, after which it was reduced by about 50%. The effect of BrdU incorporation on the activities of several enzymes with rapid turnover rates was examined to test the hypothesis that the synthesis of such enzymes will be preferentially inhibited by BrdU. Tyrosine amino-transferase (TAT) activity decreased by 70% within two generations whereas thymidine kinase activity remained at control values. PEP carboxykinase activity was unchanged during the first generation in BrdU-containing medium but, during the second, its activity increased by at least 30%. Ornithine decarboxylase levels decreased by about 50% only after two generations in the presence of BrdU. There appeared to be no simple relationship between turnover rates and the effect of BrdU on enzyme activity. Incorporation of BrdU was found to inhibit the induction of both TAT and PEP carboxykinase by dexamethasone and to enhance the inhibition of cell growth by this steroid. These results are discussed with respect to possible mechanisms of gene expression and development in both normal and neoplastic cells.
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PMID:The diverse effects of 5'-bromodeoxyuridine on enzyme activities in cultured H35 hepatoma cells. 1 36

After partial hepatectomy in rats, the following changes in enzymic activities were observed in the remnant liver during the prereplicative period. In the initial period of the prereplicative process, soon after removal of part of the liver, ornithine decarboxylase [EC 4.1.1.17] and IMP dehydrogenase [EC 1.2.1.14] increase. Subsequently, for entry into the S period, thymidine kinase [EC 2.7.1.75] increases simultaneously with increase in the intracellular cyclic AMP level and decrease in its phosphodiesterase [EC 3.1.4.17].
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PMID:Prereplicative enzymic changes in regenerating rat liver. 16 85

A method for producing solid tumors in rat liver or spleen by local inoculation of Yoshida sarcoma or Hirosaki sarcoma was developed by careful selection of rat strains. After development of the tumor, the liver was isolated and perfused with a mixture of calf serum and fluorocarbon. Addition of corticoid hormone to the perfusion fluid induced tyrosine aminotransferase in normal tissue of the liver and to a lesser degree in the tumor tissue. Corticoid did not cause any detectable induction of thymidine kinase in normal tissue of the liver, but caused slight but definite induction of the enzyme in the tumor tissue. Ornithine decarboxylase was induced in the normal tissue by perfusion with serum alone, even without corticoid, but no enzyme induction was observed in the tumor tissue. The low level of this enzyme found in solid tumor tissue might be due to the fact that the enzyme was measured in the late period of tumor growth, because, in experiments with ascites tumor cells, higher enzyme activities were observed in the early period of growth.
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PMID:Induction of ornithine decarboxylase, tyrosine aminotransferase, and thymidine kinase by glucocorticoid in isolated, perfused liver after tumor inoculation. 24 80

Rats were entrained to a 12 h dark/12 h light cycle with food (60% protein +/- 0.5% butylated hydroxytoluene or 0.05% phenobarbital) available only during the first 2 h of the dark period. Under these conditions liver ornithine decarboxylase (ODC) activity in control animals displayed a characteristic diurnal oscillation. In livers of rats fed butylated hydroxytoluene or phenobarbital ODC activity was not increased whereas thymidine kinase (TK) activity was stimulated 4--10 fold at 3 days. In lungs from the same animals ODC and TK activities were unchanged. In rats fed butylated hydroxytoluene for 3 days [3H]thymidine incorporation into DNA was increased in liver but decreased in lung.
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PMID:Effects of dietary butylated hydroxytoluene and phenobarbital on the activities of ornithine decarboxylase and thymidine kinase in rat liver and lung. 68 94

The immunological properties of thymidine kinase from a variety of human tumors suggest that the form of the tumor enzyme resembles that found in the placenta and in the nondividing colonic flat mucosa. To examine the placenta-like characteristics of tumor thymidine kinase, the jejunum and colon from rats ranging in age from fetal to old and from animals treated with dimethylhydrazine (DMH), an intestinal carcinogen, have been studied. In normal jejunum, thymidine kinase activity decreased rapidly with age. Both the activity and the response to phospholipase C and to mercaptans in DMH-induced tumors resembled that of fetal gut, while those in abnormal appearing DMH-treated jejunum were intermediate between normal control of the same age and tumor. Similar but less pronounced changes were seen in the colon. In the jejunum, the level of another enzyme normally associated with rapid cell division, ornithine decarboxylase, was found to be over 100 times that of the liver, colon, and stomach. Treatment of the animals with acetylaminofluorene and with DMH resulted in elevated levels of the enzyme in liver and in colon, respectively, but had little effect on this enzyme in other tissues. The data presented indicate that there were premalignant changes in the levels of both of these enzymes in target tissues of animals treated with carcinogens.
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PMID:Biochemical changes in premalignant intestines. 97 9

Two enzymes were examined as potential indicators of early precancerous changes. Ornithine decarboxylase, an enzyme normally associated with rapid cell division, is low in the rapidly dividing, cancer-susceptible colon. The level of this enzyme was also very high in the nondividing cells of the small intestines. Administration of an intestinal carcinogen, dimethylhydrazine, led to a large increase in colonic ornithine decarboxylase but did not affect the enzyme in liver. A liver carcinogen, acetylaminofluorene, induced manyfold increases in ornithine decarboxylase of the liver but not of the colon. Studies of thymidine kinase of the gut showed that this enzyme changed quantitatively and qualitatively throughout the life of the animal, from fetal rat to newborn and adult. The tumor enzyme has many fetal-like properties. Long-term treatment with dimethylhydrazine led to changes in thymidine kinase reminiscent of the fetal enzyme. Short-term treatment caused sharp increases in the thymidine kinase of nondividing cells of the jejunum and the proximal end of the colon; similar changes in the distal end of the colon were slower in appearing and less pronounced.
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PMID:Biochemical changes in preneoplastic rodent intestines. 127 75

The mechanism of the antiproliferation effect of N1,N12-bis(ethyl)spermine (BESPM) was studied in detail using mouse FM3A cells, since this polyamine analogue mimics the functions of spermine in several aspects [Igarashi, K., Kashiwagi, K., Fukuchi, J., Isobe, Y., Otomo, S. & Shirahata, A. (1990) Biochem. Biophys. Res. Commun. 172, 715-720]. Our results indicate that not only the decrease in sperimine and spermine caused by BESPM but also its accumulation play important roles on the inhibition of cell growth by BESPM, since BESPM accumulated in cells at a concentration fivefold that of spermidine in control cells. In comparison with the polaymine-deficient cells caused by alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase, and ethylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, the behavior of polyamine-deficient cells caused by BESPM was different as follows: the inhibition of cell growth by BESPM was not abrogated by spermine or spermidine; polyamine uptake, which is stimulated during polyamine deficiency, was greatly inhibited, while spermidine/spermine N1-acetyltransferase activity, which is inhibited during polyamine deficiency, was enhanced in BESPM-treated cells; thymidine kinase activity did not decrease in BESPM-treated cells; inhibition of cell growth and macromolecule synthesis by BESPM correlated with the swelling of mitochondria and the decrease in ATP content; BESPM caused cell death when incubated together for several days. The role of BESPM accumulation on inhibition of cell growth is discussed.
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PMID:Mechanism of the inhibition of cell growth by N1,N12-bis(ethyl)spermine. 142 76

The expression of a set of cell cycle dependent (CCD) genes (c-fos, c-myc, ornithine decarboxylase (ODC), and thymidine kinase (TK)) was comparatively studied in cultured arterial smooth muscle cells (SMC) during exit from quiescence and exponential proliferation. These genes, which were not expressed in quiescent SMC, were chronologically induced after serum stimulation. c-fos mRNA were rapidly and transiently expressed very early in the G1 phase; c-myc and ODC peaked a few hours after serum stimulation and then remained at an intermediary level throughout the first cell cycle; TK mRNA and activity then appeared at the G1/S boundary and peak in G2/M phases. Except for c-fos, the other genes were also expressed in asynchronously cycling SMC (ACSMC); their expression was studied in elutriated subpopulations representative of cell cycle progression. c-fos mRNA were undetectable in any sorted subpopulations, even in the pure early G1 population. Despite a slight increase as the cell cycle advanced, c-myc and ODC genes were expressed throughout the ACSMC cell cycle. A faint TK activity was found in G1 subpopulations and increased in populations enriched in other phases; in contrast, TK mRNA remained highly expressed in all elutriated subpopulations. This study demonstrates significant modulations in CCD gene expression between quiescent stimulated and asynchronously cycling SMC in culture. This suggests that the events occurring during the emergence of SMC from quiescence are probably different from those in the G1 phase of ACSMC.
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PMID:Cell cycle dependent gene expression in quiescent stimulated and asynchronously cycling arterial smooth muscle cells in culture. 153 80

Experiments performed in different models of hepatic regeneration at the time of maximal DNA synthesis, determined by thymidine kinase activity assay, demonstrated that spermidine N8-acetyltransferase activity increased 48 hr after CCl4 administration (2-fold), 72 hr after CCl4 plus phenobarbital (3-fold) and 24 hr after partial hepatectomy (4.5-fold). On the contrary, at these times histone acetyltransferase activity diminished (approximately twofold) and was unchanged compared with control values in the liver of hepatotoxin-treated and hepatectomized rats, respectively. Histone acetylation was, however, enhanced 1.5-fold before the onset of DNA replication (14 hr), and 3.4-fold after the peak of DNA synthesis (32 hr) in the liver of hepatectomized rats. alpha-Difluoromethylornithine, a specific and irreversible inhibitor of ornithine decarboxylase that was administered to hepatectomized rats, blocked polyamine synthesis, thymidine kinase activity and consequently liver regeneration 24 hr after the surgery. In those conditions, spermidine N8-acetyltransferase activity was decreased approximately twofold, whereas histone acetyltransferase activity was elevated approximately twofold. All these effects were reversed by putrescine coadministration. Altogether, these findings showed that nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities were regulated in opposite ways during the processes associated with liver regeneration. Moreover, they suggested that the polyamines themselves might have a direct or indirect role in this regulation.
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PMID:Opposite responses of nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities to regenerative stimuli in rat liver. 156 34


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