Carcinogenesis Advance Access published online on October 7, 2004
Carcinogenesis, doi:10.1093/carcin/bgh295
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institute of Zoology, Academia Sinica, Taipei 115, Taiwan, Republic of China
* To whom correspondence should be addressed. E-mail: lhyih{at}gate.sinica.edu.tw.
Arsenic compounds, which are well-documented human carcinogens, are now used in cancer therapy. Knowledge of the mechanism by which arsenic exerts its toxicity may help in designing a more effective regimen for therapy. In this study, we showed that arsenite could induce prominent mitotic arrest in CGL-2 cells and demonstrated the presence of damaged DNA in arsenite-arrested mitotic cells. We then explored why these cells with arsenite-induced DNA damage were arrested at mitosis instead of G2 stage. When synchronized CGL-2 cells were treated with arsenite at stage G1, S, or G2, all progressed into, and arrested at, the mitotic stage and contained damaged DNA, as demonstrated by the appearance of the DNA double strand break marker, phosphorylated histone H2A.X (
Revised August 27, 2004
Accepted September 27, 2004
CANCER BIOLOGY
Arsenite induces prominent mitotic arrest via inhibition of G2 checkpoint activation in CGL-2 cells
2 Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien 970, Taiwan, Republic of China
3 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China
Abstract 
-H2AX). Since X-irradiation induced G2 arrest in CGL-2 cells, these cells clearly have a functional G2 DNA damage checkpoint. However, treatment of X-irradiated CGL-2 cells with arsenite resulted in a decrease in G2 cells and an increase in mitotic cells, suggesting that arsenite may inhibit activation of the G2 DNA damage checkpoint and thus allow cells with damaged DNA to proceed from G2 into mitosis. Immunoblot analysis confirmed that arsenite treatment reduced the X-irradiation-induced phosphorylation of both ATM at serine 1981 and Cdc25C at serine 216, events which are crucial for G2 checkpoint activation and G2 arrest. Moreover, higher frequency of apoptotic cells is observed in mitotic CGL-2 cells arrested by arsenite than those arrested by nocodazole or taxol. Our results show that the combined effects of arsenite in inducing DNA damages, inhibiting the activation of G2 checkpoint, and arresting cells with damaged DNA in the mitotic stage may subsequently enhance the induction of apoptosis in arsenite-arrested mitotic CGL-2 cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K.-H. Kim, J.-Y. Jeong, Y.-J. Surh, and K.-W. Kim Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes Nucleic Acids Res., October 28, 2009; (2009) gkp865v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Zykova, F. Zhu, C. Lu, L. Higgins, Y. Tatsumi, Y. Abe, A. M. Bode, and Z. Dong Lymphokine-Activated Killer T-Cell-Originated Protein Kinase Phosphorylation of Histone H2AX Prevents Arsenite-Induced Apoptosis in RPMI7951 Melanoma Cells Clin. Cancer Res., December 1, 2006; 12(23): 6884 - 6893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Lu, K.-W. Chang, C.-J. Liu, Y.-H. Tseng, H.-H. Lu, S.-Y. Lee, and S.-C. Lin Ripe areca nut extract induces G1 phase arrests and senescence-associated phenotypes in normal human oral keratinocyte Carcinogenesis, June 1, 2006; 27(6): 1273 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-H. Yih, Y.-Y. Tseng, Y.-C. Wu, and T.-C. Lee Induction of Centrosome Amplification during Arsenite-Induced Mitotic Arrest in CGL-2 Cells Cancer Res., February 15, 2006; 66(4): 2098 - 2106. [Abstract] [Full Text] [PDF]
|
|