SELECTIVE INDUCTION OF APOPTOSIS OF NB4 CELLS FROM G(2)+M PHASE BY SODIUM ARSENITE AT LOWER DOSES

Apoptosis of NE4 cells induced by sodium arsenite and arsenate was stu died using flow cytometry and DNA gel electrophoresis in order to inve stigate their effects on cell cycle and determine the relationship bet ween apoptosis and cell cycle. In this study, we found that: 1) at low doses, sodium arsenite selectively induced apoptosis of NE4 cells in G(2)+M phase of cell cycle after its being arrested in G(2), phase. Wi th increment of the cells blocked in G(2), phase, dUTP-specifically la beling cells in G(2)+M phase increased without concomitant increment o f dUTP-labeling cells in other two phases of cell-cycle; 2) at high do ses, extensive apoptosis was induced in NE, cells from all phases of c ell cycle without cell cycle preference and cell cycle blockade; 3) so dium arsenite-induced apoptosis of NB4, cells occurred in the presence of bcl-2 expression as the unapoptotic cells; 4) sodium arsenite with As3+ induced apoptosis of NE, cells more strongly than sodium arsenat e with As5+ did although both of them affected NE4, cells in the same pattern. These results not only suggested that both arsenite and arsen ate induced apoptosis of NE4 cells through 2 different mechanisms - at low doses, arsenical might directly induce apoptosis through regulati on of cell cycle checkpoint, while at high doses they might directly i nduce it, but also indicated that bcl-2 might not play an important ro le in arsenite or arsenate induced apoptosis of NE4 cells, whereas che mical valence of As in a compound might be related to efficiency in ar senical induction of apoptosis.