5-氟尿嘧啶和5-氟-2'-脱氧尿苷在诱导L1210白血病细胞致死性方面遵循不同的代谢途径。

5-fluorouracil and 5-fluoro-2'-deoxyuridine follow different metabolic pathways in the induction of cell lethality in L1210 leukaemia.

作者信息

Roobol C, De Dobbeleer G B, Bernheim J L

出版信息

Br J Cancer. 1984 Jun;49(6):739-44. doi: 10.1038/bjc.1984.116.

DOI:10.1038/bjc.1984.116

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1976839/

Abstract

The mode of action of 5-fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd) on L1210 leukaemia has been studied. It is shown that FUra and FdUrd follow different routes of metabolism and have different targets with respect to their cytotoxic activity. FUra is converted to 5-fluorouridine-5'triphosphate ( FUTP ), which is incorporated into nascent RNA. FdUrd is converted to 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), which inhibits the de novo synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP). Conversion of FUra to FdUMP does occur, but this phenomenon does not contribute to the final cytotoxic effect. No conversion of FdUrd to FUra has been detected.

摘要

对5-氟尿嘧啶（FUra）和5-氟-2'-脱氧尿苷（FdUrd）作用于L1210白血病的作用方式进行了研究。结果表明，FUra和FdUrd在代谢途径和细胞毒性活性靶点方面存在差异。FUra转化为5-氟尿苷-5'-三磷酸（FUTP），并掺入新生RNA中。FdUrd转化为5-氟-2'-脱氧尿苷-5'-单磷酸（FdUMP），它抑制2'-脱氧胸苷-5'-单磷酸（dTMP）的从头合成。FUra确实会转化为FdUMP，但这种现象对最终的细胞毒性作用没有贡献。未检测到FdUrd转化为FUra。

相似文献

1

5-fluorouracil and 5-fluoro-2'-deoxyuridine follow different metabolic pathways in the induction of cell lethality in L1210 leukaemia.5-氟尿嘧啶和5-氟-2'-脱氧尿苷在诱导L1210白血病细胞致死性方面遵循不同的代谢途径。

Br J Cancer. 1984 Jun;49(6):739-44. doi: 10.1038/bjc.1984.116.

2

Alteration of fluorouracil metabolism in human colon cancer cells by dipyridamole with a selective increase in fluorodeoxyuridine monophosphate levels.双嘧达莫对人结肠癌细胞中氟尿嘧啶代谢的影响，伴氟脱氧尿苷一磷酸水平选择性升高。

Cancer Res. 1986 Dec;46(12 Pt 1):6191-9.

3

Tumor-selective metabolism of 5-fluoro-2'-deoxycytidine coadministered with tetrahydrouridine compared to 5-fluorouracil in mice bearing Lewis lung carcinoma.与5-氟尿嘧啶相比，在携带Lewis肺癌的小鼠中，5-氟-2'-脱氧胞苷与四氢尿苷共同给药时的肿瘤选择性代谢。

Cancer Res. 1987 May 1;47(9):2354-62.

4

Assignment and pH dependence of the 19F-NMR resonances from the fluorouracil anabolites involved in fluoropyrimidine chemotherapy.氟嘧啶化疗中涉及的氟尿嘧啶同化产物的¹⁹F-NMR共振的归属及pH依赖性

NMR Biomed. 1999 Jun;12(4):237-48. doi: 10.1002/(sici)1099-1492(199906)12:4<237::aid-nbm565>3.0.co;2-0.

5

Modulation of 1-beta-D-arabinofuranosylcytosine metabolism and cytotoxicity in L1210 cells by fluoropyrimidine pretreatment.氟嘧啶预处理对L1210细胞中1-β-D-阿拉伯呋喃糖基胞嘧啶代谢及细胞毒性的调节作用。

Cancer Res. 1982 Sep;42(9):3550-6.

6

Differential selectivity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in cultured human B lymphocytes and mouse L1210 leukemia.5-氟尿嘧啶和5'-脱氧-5-氟尿苷在培养的人B淋巴细胞和小鼠L1210白血病细胞中的差异选择性

Biochem Pharmacol. 1983 Feb 1;32(3):541-6. doi: 10.1016/0006-2952(83)90536-1.

7

Biologic effect of 5-fluoro-2'-deoxyuridine incorporation in L1210 deoxyribonucleic acid.

Biochem Pharmacol. 1983 Apr 15;32(8):1337-40. doi: 10.1016/0006-2952(83)90443-4.

8

Determinants of cytotoxicity with prolonged exposure to fluorouracil in human colon cancer cells.人结肠癌细胞长期暴露于氟尿嘧啶时细胞毒性的决定因素。

Oncol Res. 1997;9(2):77-88.

9

Isolation and characterization of a human ileocecal carcinoma cell line (HCT-8) subclone resistant to fluorodeoxyuridine.

Biochem Pharmacol. 1993 Mar 9;45(5):1157-64. doi: 10.1016/0006-2952(93)90262-u.

10

Nucleotide levels and incorporation of 5-fluorouracil and uracil into DNA of cells treated with 5-fluorodeoxyuridine.用5-氟脱氧尿苷处理的细胞中核苷酸水平以及5-氟尿嘧啶和尿嘧啶掺入DNA的情况。

Mol Pharmacol. 1982 Jan;21(1):211-6.

引用本文的文献

1

Drug repurposing for the treatment of staphylococcal infections.药物重新利用用于治疗葡萄球菌感染。

Curr Pharm Des. 2015;21(16):2089-100. doi: 10.2174/1381612821666150310104416.

2

The role of fluorinated pyrimidine analogues in the induction of the in vitro expression of the fragile X chromosome.氟代嘧啶类似物在诱导脆性X染色体体外表达中的作用。

Hum Genet. 1988 Aug;79(4):341-6. doi: 10.1007/BF00282173.

3

Intracellular localization of drugs in cultured tumor cells by ion microscopy and image processing.通过离子显微镜和图像处理技术对培养肿瘤细胞中药物的细胞内定位研究

Histochemistry. 1990;93(4):397-400. doi: 10.1007/BF00315857.

本文引用的文献

1

THE MODE OF ACTION OF 5-FLUOROURACIL AND ITS DERIVATIVES.5-氟尿嘧啶及其衍生物的作用模式。

Proc Natl Acad Sci U S A. 1958 Oct 15;44(10):1004-12. doi: 10.1073/pnas.44.10.1004.

2

Studies on fluorinated pyrimidines. XIII. Inhibition of thymidylate synthetase.氟化嘧啶的研究。十三。胸苷酸合成酶的抑制作用。

J Biol Chem. 1961 Nov;236:3006-13.

3

Enzymic ribosidation and ribotidation of 5-fluorouracil by extracts of the Ehrlich-ascites tumor.

Biochim Biophys Acta. 1958 Sep;29(3):651. doi: 10.1016/0006-3002(58)90029-5.

4

Studies on fluorinated pyrimidines. III. The metabolism of 5-fluorouracil-2-C14 and 5-fluoroorotic-2-C14 acid in vivo.氟化嘧啶的研究。III. 5-氟尿嘧啶-2-C14和5-氟乳清酸-2-C14在体内的代谢

Cancer Res. 1958 Apr;18(3):318-28.

5

The effect of 5-fluorouracil on the synthesis and methylation of low molecular weight nuclear RNA in L1210 cells.5-氟尿嘧啶对L1210细胞中低分子量核RNA合成及甲基化的影响。

Mol Pharmacol. 1980 Mar;17(2):245-9.

6

5-Fluorouracil incorporation into human breast carcinoma RNA correlates with cytotoxicity.5-氟尿嘧啶掺入人乳腺癌RNA与细胞毒性相关。

J Biol Chem. 1981 Oct 10;256(19):9802-5.

7

5-Fluoro-2'-deoxyuridine incorporation in L1210 DNA.5-氟-2'-脱氧尿苷掺入L1210 DNA中。

J Biol Chem. 1981 Sep 10;256(17):8885-8.

8

Specificity of pyrimidine nucleoside phosphorylases and the phosphorolysis of 5-fluoro-2'-deoxyuridine.嘧啶核苷磷酸化酶的特异性及5-氟-2'-脱氧尿苷的磷酸解作用

Cancer Res. 1980 Mar;40(3):507-11.

9

Rate of DNA synthesis in exponentially growing cell lines in the presence and absence of antimetabolites.

Anal Biochem. 1983 Aug;133(1):136-41. doi: 10.1016/0003-2697(83)90234-8.

10

5-Fluorouracil incorporation in DNA of human breast carcinoma cells.5-氟尿嘧啶掺入人乳腺癌细胞的DNA中。

Cancer Res. 1982 Aug;42(8):3005-9.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

文档翻译

学术文献翻译模型，支持多种主流文档格式。