| Proliferation inhibition, DNA damage, and cell-cycle arrest of human astrocytoma cells after acrylamide exposure. | |
| | |
MedLine Citation:
|
PMID: 20734998 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Jong-Hang Chen; Tsui-Chun Tsou; Ing-Ming Chiu; Chin-Cheng Chou |
Related Documents
:
|
8790838 - Cell cycle expression of p53 protein, c-myc gene product and tyrosine-phosphorylation l... 19189638 - Role of caspases in 5-fu and selenium-induced growth inhibition of colorectal cancer ce... 12095638 - Induction of p73beta by a naphthoquinone analog is mediated by e2f-1 and triggers apopt... 11880548 - Induction of micronuclei in human cell lines and primary cells by combination treatment... 312248 - A suppressor cell in the response of rabbit t cells to con a. 2859698 - A method for flow cytometric cell cycle analysis of normal and psoriatic human epidermi... |
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 |
Affiliation:
|
Department of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acrylamide
/
chemistry,
toxicity* Astrocytes / drug effects* Astrocytoma 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 Humans Protein-Serine-Threonine Kinases / metabolism Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins / metabolism |
| Chemical | |
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 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A modified physiological BCS for prediction of intestinal absorption in drug discovery.
Next Document: Self-propagating molecular assemblies as interlayers for efficient inverted bulk-heterojunction sola...