[Effect of agents changing the intracellular level of reactive oxygen species on the cell cycle phase distribution in 3T3 and 3T3SV40 cell lines].
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.
Gamaleĭ
I A
IA
Institute of Cytology RAS, St. Petersburg. igamaley@mail.cytspb.rssi.ru
Aksenov
N D
ND
Efremova
T N
TN
Kirpichnikova
K M
KM
D016475:3T3 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000096:biosynthesis; D051379:Mice; D011761:Pyrrolidonecarboxylic Acid; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013844:Thiazoles; D053778:Thiazolidines; D019328:Buthionine Sulfoximine; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; D000111:Acetylcysteine; C029536:2-oxothiazolidine-4-carboxylic acid