Gamaleĭ I A, Aksenov N D, Efremova T N, Kirpichnikova K M
Institute of Cytology RAS, St. Petersburg.
Tsitologiia. 2003;45(1):26-33.
A comparison of cell cycle phase distribution of 3T3 cells and their transformants 3T3SV40 treated with different substances changing the intracellular level of reactive oxygen species (ROS) has been made. In this study the following glutathione synthesis modulating agents were tested: two precursors of intracellular glutathione, antioxidant N-acetyl-L-cysteine (NAC) (-)-2-oxo-4-thiazolidine-carboxylic acid (OTZ), and inhibitor of glutathione synthesis, DL-buthionine-S, R-sulfoximine (BSO). It has been shown that both NAC (10-20 mM) and OTZ (20 mM) decreased the intracellular level of ROS in both cell lines. OTZ was more potent than NAC. However, only NAC caused changes in cell cycle progression of both cell types in dose-dependent manner. These changes differed in 3T3 and 3T3SV40 cells. Flow cytometric analysis of cell cycle phase distribution indicated that NAC (20 mM) blocked cell cycle in the G1 phase. The G1--arrest was completely reversible after removal of NAC from the medium. NAC (10-20 mM) caused a decrease in S and G2/M phases of transformants 3T3SV40. Moreover, a part of the population died apoptoticaly. Different mechanisms of NAC effect on normal and transformed cells are discussed. It is suggested that there is no strong correlation between cell cycle progression and intracellular level of ROS.
对3T3细胞及其经不同物质处理的转化细胞3T3SV40的细胞周期阶段分布进行了比较，这些物质可改变细胞内活性氧（ROS）水平。在本研究中，测试了以下谷胱甘肽合成调节剂：两种细胞内谷胱甘肽前体、抗氧化剂N-乙酰-L-半胱氨酸（NAC）、（-）-2-氧代-4-噻唑烷羧酸（OTZ）以及谷胱甘肽合成抑制剂DL-丁硫氨酸-S，R-亚砜亚胺（BSO）。结果表明，NAC（10 - 20 mM）和OTZ（20 mM）均降低了两种细胞系中的细胞内ROS水平。OTZ比NAC更有效。然而，只有NAC以剂量依赖方式引起两种细胞类型的细胞周期进程变化。这些变化在3T3细胞和3T3SV40细胞中有所不同。细胞周期阶段分布的流式细胞术分析表明，NAC（20 mM）使细胞周期在G1期停滞。从培养基中去除NAC后，G1期停滞完全可逆。NAC（10 - 20 mM）导致转化细胞3T3SV40的S期和G2/M期减少。此外，一部分细胞群体发生凋亡。讨论了NAC对正常细胞和转化细胞作用的不同机制。研究表明，细胞周期进程与细胞内ROS水平之间没有很强的相关性。
