Document Detail

Proliferation inhibition, DNA damage, and cell-cycle arrest of human astrocytoma cells after acrylamide exposure.
MedLine Citation:
PMID:  20734998     Owner:  NLM     Status:  MEDLINE    
Acrylamide (ACR) has been recognized as a neurological and reproductive toxin in humans and laboratory animals. This study aimed to determine the effects of ACR-induced DNA damage on cell cycle regulation in human astrocytoma cell lines. Treatment of U-1240 MG cells with 2 mM ACR for 48 h resulted in a significant inhibition of cell proliferation as evaluated by Ki-67 protein expression and MTT assay. The analysis of DNA damage with the comet assay showed that treatment of the cells with 0.5, 1, and 2 mM ACR for 48 h caused significant increases in DNA damage by 3.5-, 4-, and 14-fold, respectively. Meanwhile, analysis of cell-cycle arrest with flow cytometry revealed that the ACR treatments resulted in significant increases in the G(0)/G(1)-arrested cells in a time- and dose-dependent manner. Expression of DNA damage-associated/checkpoint-related signaling molecules, including phosphorylated-p53 (pp53), p53, p21, p27, Cdk2, and cyclin D(1), in three human astrocytoma cell lines (U-1240 MG, U-251 MG, and U-87 MG) was also analyzed by immunoblotting. Treatment of the three cell lines with 2 mM ACR for 48 h caused marked increases in pp53 and Cdk2, as well as decreases in cyclin D(1) and p27. Moreover, increases in p53 and p21 were detected in both U-1240 and U-87 MG cells, whereas no marked change in p53 and a decrease in p21 were observed in U-251 MG cells. To address the involvement of ataxia telangiectasia mutated/ATM-Rad3-related (ATM/ATR) kinase in the signaling of ACR-induced G(0)/G(1) arrest, caffeine was used to block the ATM/ATR pathway in U-1240 MG cells. Caffeine significantly attenuated the ACR-induced G(0)/G(1) arrest as well as the expression of DNA damage-associated/checkpoint-related signaling molecules in a dose-dependent manner. This in vitro study clearly demonstrates the critical role of ATM/ATR in the signaling of ACR-induced cell-cycle arrest in astrocytoma cells.
Jong-Hang Chen; Tsui-Chun Tsou; Ing-Ming Chiu; Chin-Cheng Chou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  23     ISSN:  1520-5010     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-20     Completed Date:  2011-01-18     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1449-58     Citation Subset:  IM    
Department of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
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MeSH Terms
Acrylamide / chemistry,  toxicity*
Astrocytes / drug effects*
Cell Cycle / drug effects*
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Comet Assay
Cyclin D1 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
DNA Damage*
DNA-Binding Proteins / metabolism
G0 Phase / drug effects
G1 Phase / drug effects
Protein-Serine-Threonine Kinases / metabolism
Tumor Suppressor Protein p53 / metabolism
Tumor Suppressor Proteins / metabolism
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA-Binding Proteins; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 136601-57-5/Cyclin D1; 79-06-1/Acrylamide; EC 2.7.1.-/ATR protein, human; EC Kinases; EC telangiectasia mutated protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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