Document Detail

Effect of cadmium on cell cycle progression in Chinese hamster ovary cells.
MedLine Citation:
PMID:  15501434     Owner:  NLM     Status:  MEDLINE    
Chinese hamster ovary K1 (CHO K1) cells are very sensitive to cadmium (Cd) toxicity. They were used to investigate the effect of Cd on cell cycle progression. Cells were cultured with 0.1, 0.4, 1 or 4 microM Cd for various time intervals. There was no difference in growth rate when less than 0.4 microM Cd was given within 24 h. A dose-dependent reduction of cell proliferation was observed when more than 0.4 microM of Cd was given. The cells were pulse-labeled with 5-bromodeoxyuridine (BrdU), and the labeled cells were cultured in the presence of increasing concentrations of Cd. Cell cycle progression was retarded as a function of Cd concentration. G2/M arrest was observed when the BrdU-labeled cells were treated with 1 microM Cd for 8h, whereas cells receiving 4 microM Cd stopped at the S phase within 4 h. Cell cycle analysis of cells treated with Cd for 24 h showed that G2/M arrest occurred only when cells received 0.8 to 2 microM Cd. Despite the occurrence of G2/M arrest in the Cd treatment, only a limited proportion of the cells were blocked in the M phase. However, the increase in M phase cells coincided with an elevation in the cyclin-dependent kinase 1 activity. To examine whether Cd acts on cells at a specific cell stage, they were synchronized at the G1 or G2/M phase then treated with 1 microM Cd for 12 h. The cells were blocked at the G2/M and G1/S phase, respectively. This finding indicates that Cd toxicity is global and not cell phase specific. We also investigated the involvement of Cd-induced reactive oxygen species (ROS) with the occurrence of G2/M block and found a lack of correlation between cell cycle arrest and ROS production. We measured the Cd content that caused G2/M arrest from a series of Cd treatments and determined the ranges of cumulative Cd concentrations that could result in cell cycle arrest.
Pei-Ming Yang; Shu-Jun Chiu; Kwei-Ann Lin; Lih-Yuan Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  149     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-25     Completed Date:  2005-01-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  125-36     Citation Subset:  IM    
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, ROC.
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MeSH Terms
Blotting, Western
Bromodeoxyuridine / metabolism
CDC2 Protein Kinase / metabolism
CHO Cells / cytology,  drug effects*,  metabolism
Cadmium / toxicity*
Cell Cycle / drug effects*
Cell Proliferation / drug effects
Flow Cytometry
Reactive Oxygen Species / metabolism
Reg. No./Substance:
0/Reactive Oxygen Species; 59-14-3/Bromodeoxyuridine; 7440-43-9/Cadmium; EC Protein Kinase

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