• Title/Summary/Keyword: thymidine

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Effects of Thymidine Anologs on Methyl Methaesulfonate Induced Chromosome Aberrations in Human Lymphocytes in Vitro (Methyl Methanesulfonata에 의한 사람의 培養細胞 染色體에 미치는 Thymidine 相似體의 影響)

  • Kang, Yung-Sun;Park, Sang-Dai;Park, Kyung-Hee
    • The Korean Journal of Zoology
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    • v.19 no.2
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    • pp.71-78
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    • 1976
  • Chromosome aberration induced by methyl methanesulfonate (MMS) and the effects of thymidine analogs (BUdR or IUdR) on MMS-induced chromosome aberration were studied in human lymphocyte cultures. Single treatment with MMS to lymphocytes induces both chromatid and chromosome type aberrations with high frequency of chromatid type. The combined treatment of BUdR or IUdR with MMS was found to be more effective in increasing the rate of chromosome type aberrations.

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3′-deoxy-3′-heterocyclic thio thymidine 유도체의 합성

  • 김득준;안순길
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.116-116
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    • 1993
  • 전 세계적으로 문제가 되고 있는 질병인 AIDS의 원인 virus인 HIV에 활성이 있는 nucleoside 유도체를 개발하기 위해, 일반적으로 HIV에 활성이 있는 3'-deoxythymidine 유도체의 일종으로써 3'-위치에 hydroxy기 대신에 heterocyclic thio기가 치환된 3'-deoxy-3' -(pyrimidin-2-yl)thio thymidine 및 3'-deoxy-3'-(1-methyltetrazol-5-yl) thiothymidine을 thymidine을 출발물질로 각각 합성하였다. 그러나 이 두 화합물은 항 HIV-1 (CEM cell line)에 대하여 활성이 없었다.

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Nuclear Imaging of Cellular Proliferation (핵의학적 세포증식 영상)

  • Yeo, Jeong-Seok
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.198-204
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    • 2004
  • Tumor cell proliferation is considered to be a useful prognostic indicator of tumor aggressiveness and tumor response to therapy but in vitro measurement of individual proliferation is complex and tedious work. PET imaging provides a noninvasive approach to measure tumor growth rate in situ. Early approaches have used $^{18}F$-FDG or methionine to monitor proliferation status. These 2 tracers detect changes in glucose and amino acid metabolism, respectively, and therefore provide only an indirect measure of proliferation status. More recent studies have focused on DNA synthesis itself as a marker of cell proliferation. Cell lines and tissues with a high proliferation rate require high rates of DNA synthesis. $[^{11}C]Thymidine$ was the first radiotracer for noninvasive imaging of tumor proliferation. The short half-life of $^{11}C$ and rapid metabolism of $[^{11}C]Thymidine$ in vivo make the radiotracer less suitable for routing use. Halogenated thymidine analogs such as 5-iodo-2-deoxyuridine (IUdR) can be successfully used as cell proliferation markers for in vitro studies because these compounds are rapidly incorporated into newly synthesized DNA. IUdR has been evaluated as a potential in vivo tracer in nuclear medicing but the image qualify and the calculation of proliferation rates are impaired by its rapid in vivo degradation. Hence, the thymidine analog $3'-deoxy-3'-^{18}F-fluorothymidine$ (FLT) was recently introduced as a stable proliferation marker with a suitable nuclide half-life and stable in vivo. $[^{18}F]FLT$ is phosphorylated to 3-fluorothymidine monophosphate by thymidine kinase 1 and reflects thymidine kinase 1 activity in proliferating cell. $[^{18}F]FLT$ PET is feasible in clincal use and well correlates with cellular proliferation. Choline is a precursor for the biosynthesis of phospholipids (in particular, phosphatidylcholine), which is the essential component of all eukaryotic cell membranes and $[^{11}C]choline$, which is a new marker for cellular proliferation.

Cell cycle-dependent entry of Toxoplasma gondii into synchronized HL-60 cells (세포 주기 변화에 따른 Toxoplasmu gondii의 침투 양상)

  • 윤지혜;남호우
    • Parasites, Hosts and Diseases
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    • v.29 no.2
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    • pp.121-128
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    • 1991
  • The degree of attraction of Toxoplasma gondii to vertebrate cells varies with cell type and cell phase. Human promyelocytic leukemia cells, HL-60, were synchronized by double thymidine block method and co-cultured with Toxoplasma for 1 hr at each cell stage to investigate the cell cycle specific susceptibility of parasites to host cells. For 30 hr the average number of Texoplasma that invaded was a little changed except at 3 hr from G1/S phase boundary which concurred with the peak point of DNA synthesis. At 3 hr which is a relatively short interval compared to whole S phase, modification of cells by parasitic invasion was most remarkable. The number of Toxoplasma that penetrated was increased to more than sin times. The shape of the cells became sludgy and almost indiscernible by strong accessibility of parasites only for an hour of mfd-S phase. The same auctuation was also observed at the second peak of S phase but weakly. This suggests that there be surface molecules concerning with the attachment of Texoplasma to the host cells, which is expressed at special point of S phase. further studies on the specific protein or similar molecules related could be carried out using synchronized HL-60 cells.

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In vitro Mouse Lymphoma Thymidine Kinase (tk+/-) Gene Forward Mutation Assay in Mammalian cells (포유동물세포의 Forward Mutation을 지표로 한 Mouse Lymphoma Thymidine Kinase (tk+/-) Gene Assay)

  • 류재천;김경란;최윤정
    • Environmental Mutagens and Carcinogens
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    • v.19 no.1
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    • pp.7-13
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    • 1999
  • The mouse lymphoma thymidine kinase (tk+/-) gene assay (MOLY) using L5178Y tk+/- mouse lymphoma cell line is one of the mammalian forward mutation assays. It is well known that MOLY has many advantages and more sensitive than the other mammalian forward mutation assays such as x-linked hyposanthine phosphoribosyltransferase (hprt) gene assay. The target gene of MOLY is a heterozygous tk+/- gene located in 11 chromosome of L5178Y tk+/- cell, so it is able to detect the wide range of genetic changes like point mutation, deletion, rearrangement, and mitotic recombination within tk gene or deletion of entire chromosome 11. MOLY has relatively short expression time (2-3 days) compared to 1 week of hprt gene assay. MOLY can also induce relatively high mutant frequency so a large number of events can be recorded. The bimodal distribution of colony size which may indicate gene mutation and chromosome breakage potential of chemicals according to mutation scale such as large normal-growing mutants and small slow-growing mutants can be observed in this assay. The statistical analysis of data can be performed using the MUTANT program developed by York Electronic Research in association with Hazelton as recommended by the UKEMS (United Kingdom Environmental Mutagen Society) guidelines. This report reviewed MOLY using the microtiter cloning technique (microwell assay).

Crystallization and Preliminary X-ray diffraction Studies of Salmonella typhimurium Deoxy-Thymidine Diphosphate-D-Glucose-4, 6-Dehydratase (Salmonella typhimurium의 Deoxy-Thymidine Diphosphate-D-Glucose-4, 6-Dehydratase의 결정화와 X-선 회절에 관한 연구)

  • 최희욱;박교선
    • Korean Journal of Crystallography
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    • v.7 no.2
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    • pp.120-125
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    • 1996
  • Single crystals of deoxy-thymidine diphosphate-D-gluxose-4,6-dehydratase(abbreviated as dTDP-D-glucose dehydratase) from Escherichia coli Strain BL21 clone which harbors the gene of dTDP-D-glucose dehydratase in Salmonella typhimurium LT2 have been grown with and whithout substrates by sitting drop vapor diffusion at room temperature. The precipitating agent was 1.6 to 2.0 M Na, K phosphate buffer(pH 8.0). The crystals diffract to at least 2.5Å and belong to the hexagonal space group P61 with cell dimensions a=b=168.54Å, c=81.08Å. The asymmetric unit contains one dimer with a crystal volume per protein mass(VM) of 2.4Å3/Da and solvent content (Vsol) of 64% by volume.

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Effects of Polyunsaturated Fatty Acids on Intestinal Cell Proliferation

  • Wang, Soo-Gyoung
    • Preventive Nutrition and Food Science
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    • v.4 no.3
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    • pp.203-208
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    • 1999
  • The effect of the polyunsaterated fatty acids, linoleic acid(LA), arachidonic acid(AA) and conjugated dienoic linoleic acid(CLA) on IEC-6 cells (rat intestinal cell)proliferation and cell transduction have been determined in vitro. IEC-6 cells proliferation was assessed by cell growth and [3H]-thymidine incroporation analysis. At 10 μM concentration , the proliferationof cells supplemented with AA or LA was significantly higher than that of CLA. [3H]-thymidine uptake showed the same results. LA and AA increased [3H]-thymidine uptake more than CLA. The stimulatory effect of LA or AA was even more pronounced in the presence of IGF. Both cell number analysis and [3H]-thymidine incorporation revealed that IEC-6 cell proliferation was influenced differently by exogenous free fatty acids, in which AA or LA stimulated IEC-6 cell proliferation and CLA inhibited it. Tyorosine phosphorylation provides a key switch to regulate celluar acitivity in response to extracellular stimuli. At 20 μM and 10μM, AA with IGF-1 stimulated protein tyrosine phophorylation in IEC-6 cells, but LA's impact was less than that of AA. CLA and CLA with IGF-1 inhibited protein tyrosine phosphorylation in IEC-6 cells. These results suggest there is a possible correlation between cell proliferation and IGF receptor tyrosine knase activity driven by AA.

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Synthesis and Antitumor Activity of 2',3'-Didehydro-3'-Didehydro-3'-deoxy-thymidine and Its Derivative

  • 이봉훈;임미경;신정희;장태식;박장수;강신원
    • Bulletin of the Korean Chemical Society
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    • v.18 no.7
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    • pp.711-714
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    • 1997
  • In an effort to enhance the lipophilicities, thereby, the penetration into the cell membrane and to increase the antitumor activities of modified derivatives of 2',3'-didehydro-3'-deoxythymidine (d4T, 1), derivatives of 1 were designed and synthesized. Starting from thymidine, 1, 2',3'-didehydro-3'-deoxythymidine-5'-phosphate, disodium salt (d4T-p, 7), and two nicotinate esters of 1; 2',3'-didehydro-3'-deoxy-5'-O-(3-pyridinylcarbonyl)thymidine (d4T-NA, 5) and 2',3'-didehydro-3'-deoxy-5'-phosphoryl-O-(3-pyridinylcarbonyl)thymidine (d4T-p-NA, 8) were synthesized. The lipophilicities of the synthesized compounds were measured by P-values and antitumor activities of those were estimated against mouse leukemia P388, murine mammary carcinoma FM3A, and human histiocytic lymphoma U937 tumor cells in vitro. Although the lipophilicities of the nicotinate esters, 5 and 8 were increased 2.75- and 9.71-fold relative to that of 1 and 7, respectively, the synthesized compounds, 1, 5, 7, and 8 were found to be inactive against P388 and FM3A cells except weak antitumor activity against U937 cell.