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癌症化疗的设计:代谢调节与细胞从头合成代谢和补救代谢

The design of cancer chemotherapy: metabolic modulation and cellular de novo versus salvage metabolism.

作者信息

Rustum Y M, Takita H, Gomez G

出版信息

Antibiot Chemother (1971). 1980;28:86-93.

PMID:6998366
Abstract

Attempts were made to evaluate the degree of utilization of 'salvage' and de novo purine and pyrimidine metabolites by normal and tumor cells. The significance of unique ribonucleotide pools and their ratios were also investigated. The results indicate that while normal bone marrow cells appear to depend almost exclusively on salvage pathways for their nucleic acid synthesis, tumor cells appear to utilize both the de novo and salvage pathways. The degree of dependence of tumor cells on these pathways appears to vary considerably. Utilizing this unique difference between tumor and normal cells, attempts were made to utilize the salvage precursors with the hope of modifying selectively the effects of antimetabolites against tumor cells in vivo. Results indicate that thymidine can potentiate the in vivo toxicity of 1-beta-D-arabinofuranosylcytosine and fluorouracil. The degree of modulation by normal metabolites appears to correlate with the level of circulating salvage metabolites.

摘要

研究人员试图评估正常细胞和肿瘤细胞对“补救”以及从头合成嘌呤和嘧啶代谢物的利用程度。还研究了独特的核糖核苷酸库及其比例的意义。结果表明,正常骨髓细胞的核酸合成似乎几乎完全依赖补救途径,而肿瘤细胞似乎同时利用从头合成途径和补救途径。肿瘤细胞对这些途径的依赖程度似乎差异很大。利用肿瘤细胞与正常细胞之间的这种独特差异,研究人员尝试使用补救前体,以期在体内选择性地改变抗代谢物对肿瘤细胞的作用。结果表明,胸腺嘧啶可以增强1-β-D-阿拉伯呋喃糖基胞嘧啶和氟尿嘧啶的体内毒性。正常代谢物的调节程度似乎与循环补救代谢物的水平相关。

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