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甲氨蝶呤给药后5-氟尿嘧啶核苷酸形成增强：药物协同作用的解释。

Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism.

作者信息

Cadman E, Heimer R, Davis L

出版信息

Science. 1979 Sep 14;205(4411):1135-7. doi: 10.1126/science.472732.

DOI:10.1126/science.472732
PMID:472732
Abstract

Exposure of L1210 leukemia cells first to 0.1 to 100 micromolar methotrexate and then to 10 micromolar 5-fluorouracil produces a synergistic effect on the number of cells killed in culture. Methotrexate dose-related increases occur in the concentrations of intracellular 5-fluorouracil ribonucleotides and 5-fluoro-2'-deoxyuridylate and in the incorporation of 5-fluorouracil into RNA. These increases are correlated with increased concentrations of intracellular phosphoribosylpyrophosphate. It is proposed that the enhanced formation of ribonucleotides of 5-fluorouracil and the subsequent incorporation of these compounds into RNA in methotrexate-treated cells may account for synergism between these agents.

摘要

将L1210白血病细胞先暴露于0.1至100微摩尔的甲氨蝶呤，然后再暴露于10微摩尔的5-氟尿嘧啶，对培养中被杀灭的细胞数量产生协同效应。甲氨蝶呤剂量相关的增加发生在细胞内5-氟尿嘧啶核糖核苷酸和5-氟-2'-脱氧尿苷酸的浓度以及5-氟尿嘧啶掺入RNA的过程中。这些增加与细胞内磷酸核糖焦磷酸浓度的增加相关。有人提出，在甲氨蝶呤处理的细胞中，5-氟尿嘧啶核糖核苷酸形成的增强以及这些化合物随后掺入RNA可能解释了这些药物之间的协同作用。

相似文献

1
Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism.甲氨蝶呤给药后5-氟尿嘧啶核苷酸形成增强：药物协同作用的解释。
Science. 1979 Sep 14;205(4411):1135-7. doi: 10.1126/science.472732.
2
The influence of methotrexate pretreatment on 5-fluorouracil metabolism in L1210 cells.甲氨蝶呤预处理对L1210细胞中5-氟尿嘧啶代谢的影响。
J Biol Chem. 1981 Feb 25;256(4):1695-704.
3
Biochemical alterations during unperturbed suspension growth of L1210 cells.L1210细胞在未受干扰的悬浮生长过程中的生化改变。
Cancer Res. 1981 Jan;41(1):157-63.
4
5-fluorouracil-methotrexate synergy: enhancement of 5-fluorodeoxyridylate binding to thymidylate synthase by dihydropteroylpolyglutamates.5-氟尿嘧啶-甲氨蝶呤协同作用：二氢蝶酰多聚谷氨酸增强5-氟脱氧尿苷酸与胸苷酸合成酶的结合
Proc Natl Acad Sci U S A. 1980 Oct;77(10):5663-7. doi: 10.1073/pnas.77.10.5663.
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Pretreatment of colon carcinoma cells with Tomudex enhances 5-fluorouracil cytotoxicity.
Clin Cancer Res. 1998 Feb;4(2):469-73.
6
Tiazofurin enhances the anabolism and toxicity of 5-fluorouracil.硫唑嘌呤增强5-氟尿嘧啶的合成代谢及毒性。
Cancer Lett. 1996 Dec 3;109(1-2):49-55. doi: 10.1016/s0304-3835(96)04416-3.
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Optimal schedule of methotrexate and 5-fluorouracil in human breast cancer.甲氨蝶呤与5-氟尿嘧啶治疗人类乳腺癌的最佳给药方案
Cancer Res. 1982 May;42(5):2081-6.
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Increase of phosphoribosylpyrophosphate levels in cultured L1210 leukemia cells exposed to methotrexate.暴露于甲氨蝶呤的培养L1210白血病细胞中磷酸核糖焦磷酸水平的升高。
Adv Exp Med Biol. 1979;122B:351-6. doi: 10.1007/978-1-4684-8559-2_57.
9
The efficacy of combined therapy with methotrexate and 5-fluorouracil from the view point of cellular PRPP level of L1210 cells and HeLa S3 cells.
Sci Rep Res Inst Tohoku Univ Med. 1985 Dec;32(1-4):47-52.
10
The role of methotrexate and dihydrofolate polyglutamates in the enhancement of fluorouracil action by methotrexate.甲氨蝶呤和二氢叶酸多聚谷氨酸在甲氨蝶呤增强氟尿嘧啶作用中的作用。
Cancer Treat Rep. 1981;65 Suppl 1:29-35.

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