EFFECT OF AGENTS AFFECTING THE INTRACELLULAR LEVEL OF REACTIVE OXYGEN
SPECIES ON THE CELL CYCLE PHASE DISTRIBUTION IN 3T3 AND 3T3SV40 CELL LINES
I. A. Gamaley,1 N. D. Aksenov, T. N. Efremova, Ê. Ì. Kirpichnikova
Institute of Cytology RAS, St. Petersburg;
1 e-mail: igamaley@mail.cytspb.rssi.ru
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 n 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.
Key words: reactive oxygen species, antioxidants, glutathione, cel cycle
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