Depletion of 9L rat brain tumor cell polyamine content by treatment with D,L-alpha-difluoromethylornithine inhibits proliferation and the G1 to S transition.
Depletion of 9L rat brain tumor cell polyamine content by treatment with D,L-alpha-difluoromethylornithine inhibits proliferation and the G1 to S transition.
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通过 D,L-α-二氟甲基鸟氨酸处理消除 9L 大鼠脑肿瘤细胞多胺含量，抑制增殖和 G1 到 S 的转变。
DOI：
10.1016/0014-4827(81)90420-1
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发表时间：
1981
影响因子：
3.7
通讯作者：
Marton,LJ
中科院分区：
文献类型：
--
作者：
Seidenfeld,J;Gray,JW;Marton,LJ
鸟氨酸脱羧酶的不可逆灭活剂d，l-α-二氟甲基鸟氨酸（DFMO）在低浓度（1 mM）下抑制9 L单层培养的大鼠脑肿瘤细胞的增殖，当细胞以5 × 105/瓶的初始密度接种时，DFMO的抑制率约为对照组的25%。DFMO在处理后8 h将细胞内腐胺含量降低至对照的<5%，在处理后48 h将亚精胺含量降低至对照的<5%。由10或25 mM DFMO引起的细胞停滞可以被逆转，并通过添加外源性腐胺阻断。用DFMO预处理48 h，然后在其不存在下重新铺板的细胞不能进入指数生长，直到多胺生产恢复。在重新铺板时添加外源腐胺允许预处理的细胞在与对照相同的时间恢复指数生长。流式细胞术显示，在G1期细胞的分数增加，直到多胺积累恢复，这意味着存在的G1-S块。在6小时内重新铺板，有一个在G1的对照细胞的分数减少。这些观察结果支持的假设，9 L细胞进入S期取决于一个足够的多胺细胞内池。
d,l-α-Difluoromethylornithine (DFMO), an irreversible inactivator of ornithine decarboxylase, inhibited 9L monolayer culture rat brain tumor cell proliferation at concentrations as low as 1 mM DFMO to about 25% of control growth when cells were seeded at an initial density of 5 × 105/flask. DFMO reduced intracellular putrescine content to <5% of control by 8 h and spermidine content to <5 % of control by 48 h post-treatment. Cytostasis caused by 10 or 25 mM DFMO could both be reversed and blocked by addition of exogenous putrescine. Cells pretreated for 48 h with DFMO and then replated in its absence could not enter exponential growth until polyamine production resumed. Addition of exogenous putrescine at the time of replating allowed pretreated cells to resume exponential growth at the same time as controls. Flow cytometry revealed that the fraction of cells in G1 increased until polyamine accumulation resumed, implying the presence of a G1-S block. Within 6 h of replating, there was a decrease in the fraction of control cells in G1. These observations support the hypothesis that entry of 9L cells into S phase depends on an adequate intracellular pool of polyamines.