TY - JOUR
T1 - Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells
AU - Sun, Lijuan
AU - Wang, Xin
AU - Yao, Hua
AU - Li, Wenqi
AU - Son, Young Ok
AU - Luo, Jia
AU - Liu, Jiankang
AU - Zhang, Zhuo
PY - 2012
Y1 - 2012
N2 - Compounds that contain chromate (Cr(VI)) are well-known carcinogens that are present in both industrial settings and the environment. The mechanism of carcinogenesis associated with these compounds is not well understood. This study focused on Cr(VI)-induced cell cycle arrest in human colon adenocarcinoma DLD1 cells. Treatment of the cells with Cr(VI) at 2.5 μM caused a growth arrest at the S phase. An increase in Cr(VI) concentration enhanced the growth arrest. Superoxide dismutase did not alter the Cr(VI)-induced S phase arrest. Catalase inhibited S-cell growth, indicating that H2 O2 is an important mediator in Cr(VI)-induced S phase arrest. Electron spin resonance spin-trapping measurements showed that incubation of cells with Cr(VI) generated hydroxyl radical (•OH). Catalase inhibited •OH generation, indicating that H2 O2 was generated from cells stimulated by Cr(VI) and that H2 O2 functioned as a precursor of •OH radical generation. p53, an oxidative response transcription factor, was activated upon Cr(VI) stimulation. Inhibition of p53 by introducing small hairpin RNA decreased S phase arrest induced by Cr(VI). These results support the following conclusions: (1) reactive oxygen species (ROS) are generated in Cr(VI)-stimulated DLD1 cells; (2) among the ROS generated, H2 O2 played a major role in causing S phase arrest in DLD1 cells; and (3) ROS mediated S phase arrest through a p53-dependent pathway.
AB - Compounds that contain chromate (Cr(VI)) are well-known carcinogens that are present in both industrial settings and the environment. The mechanism of carcinogenesis associated with these compounds is not well understood. This study focused on Cr(VI)-induced cell cycle arrest in human colon adenocarcinoma DLD1 cells. Treatment of the cells with Cr(VI) at 2.5 μM caused a growth arrest at the S phase. An increase in Cr(VI) concentration enhanced the growth arrest. Superoxide dismutase did not alter the Cr(VI)-induced S phase arrest. Catalase inhibited S-cell growth, indicating that H2 O2 is an important mediator in Cr(VI)-induced S phase arrest. Electron spin resonance spin-trapping measurements showed that incubation of cells with Cr(VI) generated hydroxyl radical (•OH). Catalase inhibited •OH generation, indicating that H2 O2 was generated from cells stimulated by Cr(VI) and that H2 O2 functioned as a precursor of •OH radical generation. p53, an oxidative response transcription factor, was activated upon Cr(VI) stimulation. Inhibition of p53 by introducing small hairpin RNA decreased S phase arrest induced by Cr(VI). These results support the following conclusions: (1) reactive oxygen species (ROS) are generated in Cr(VI)-stimulated DLD1 cells; (2) among the ROS generated, H2 O2 played a major role in causing S phase arrest in DLD1 cells; and (3) ROS mediated S phase arrest through a p53-dependent pathway.
KW - Cell cycle
KW - Cell cycle checkpoints
KW - Chromium (VI)
KW - Human colon cancer
KW - Reactive oxygen species
KW - p53
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UR - http://www.scopus.com/inward/citedby.url?scp=84871310462&partnerID=8YFLogxK
U2 - 10.1615/JEnvironPatholToxicolOncol.v31.i2.20
DO - 10.1615/JEnvironPatholToxicolOncol.v31.i2.20
M3 - Article
C2 - 23216635
AN - SCOPUS:84871310462
SN - 0731-8898
VL - 31
SP - 95
EP - 107
JO - Journal of Environmental Pathology, Toxicology and Oncology
JF - Journal of Environmental Pathology, Toxicology and Oncology
IS - 2
ER -
