DL-α-二氟甲基鸟氨酸对P388/S白血病细胞中多胺和核苷酸磷酸代谢的体内效应。

In vivo effects of DL-alpha-difluoromethylornithine on the polyamine and nucleotide phosphate metabolism in P388/S leukemia cells.

作者信息

Kremmer T, Boldizsár M, Holczinger L

出版信息

Exp Cell Biol. 1986;54(1):8-15. doi: 10.1159/000163338.

Abstract

In vivo effects of DL-alpha-difluoromethylornithine (DFMO) on the metabolism of polyamines and nucleotide phosphates were monitored in P388/S leukemia cells grown intraperitoneally in BDF1 inbred male mice. Inhibiting the ornithine decarboxylase (ODC) activity DFMO depleted putrescine and spermidine to 30-50 and 50-60%, respectively, and increased spermine to 25-60% compared with the controls, when given as 2% solution in drinking water of the tumor-bearing animals. DFMO treatment caused a parallel 56% elevation of total nucleotide content in tumor cells with distinct and significant increase of some nucleotide phosphates. The most pronounced alterations were shown in the intracellular UTP (202%), CTP (103%), ADP (92%) and ATP (71%) concentrations. Changes in polyamine and nucleotide phosphate metabolisms were dependent on tumor progression. A possible explanation of the metabolic events induced by DFMO is discussed.

摘要

在BDF1近交系雄性小鼠腹腔内生长的P388/S白血病细胞中，监测了DL-α-二氟甲基鸟氨酸（DFMO）对多胺和核苷酸磷酸代谢的体内影响。当以2%溶液形式添加到荷瘤动物的饮用水中时，DFMO通过抑制鸟氨酸脱羧酶（ODC）活性，使腐胺和亚精胺分别减少至对照的30 - 50%和50 - 60%，而精胺则增加至对照的25 - 60%。DFMO处理导致肿瘤细胞中总核苷酸含量平行升高56%，同时一些核苷酸磷酸显著增加。最明显的变化表现在细胞内UTP（202%）、CTP（103%）、ADP（92%）和ATP（71%）的浓度上。多胺和核苷酸磷酸代谢的变化取决于肿瘤进展。本文讨论了DFMO诱导的代谢事件的可能解释。