Selective induction of apoptosis of NB4 cells from G2+M phase by sodium arsenite at lower doses.
Apoptosis of NB4 cells induced by sodium arsenite and arsenate was studied using flow cytometry and DNA gel electrophoresis in order to investigate their effects on cell cycle and determine the relationship between apoptosis and cell cycle. In this study, we found that: 1) at low doses, sodium arsenite selectively induced apoptosis of NB4 cells in G2+M phase of cell cycle after its being arrested in G2 phase. With increment of the cells blocked in G2 phase, dUTP-specifically labeling cells in G2+M phase increased without concomitant increment of dUTP-labeling cells in other two phases of cell cycle; 2) at high doses, extensive apoptosis was induced in NB4 cells from all phases of cell cycle without cell cycle preference and cell cycle blockade; 3) sodium 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 NB4 cells more strongly than sodium arsenate with As5+ did although both of them affected NB4 cells in the same pattern. These results not only suggested that both arsenite and arsenate induced apoptosis of NB4 cells through 2 different mechanisms--at low doses, arsenical might directly induce apoptosis through regulation of cell cycle checkpoint, while at high doses they might directly induce it, but also indicated that bcl-2 might not play an important role in arsenite or arsenate-induced apoptosis of NB4 cells, whereas chemical valence of As in a compound might be related to efficiency in arsenical induction of apoptosis.
Ma
D C
DC
Department of Experimental Medicine, Northern Hospital, Shenyang, Liaoning, China.
Sun
Y H
YH
Chang
K Z
KZ
Ma
X F
XF
Huang
S L
SL
Bai
Y H
YH
Kang
J
J
Liu
Y G
YG
Chu
J J
JJ
D017209:Apoptosis / Q000187:drug effects*; D001149:Arsenates / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000166:cytology
D001149:Arsenates; D018053:Arsenites; D019253:Proto-Oncogene Proteins c-bcl-2