Document Detail

Areca nut-induced micronuclei and cytokinesis failure in Chinese hamster ovary cells is related to reactive oxygen species production and actin filament deregulation.
MedLine Citation:
PMID:  19197989     Owner:  NLM     Status:  MEDLINE    
Epidemiological studies have shown a strong association between environmental exposure to betel quid (BQ) and oral cancer. Areca nut (AN), an ingredient of BQ, contains genotoxic and mutagenic compounds. In this study, we found that AN extract (ANE) inhibited the growth of Chinese hamster ovary cells (CHO-K1) in a dose- and time-dependent manner. Intracellular reactive oxygen species (ROS) levels and micronuclei (MN) frequency were significantly increased following ANE treatment in CHO-K1 cells. Addition of catalase markedly inhibited ANE-induced MN formation, indicating that ANE-induced genotoxicity was correlated with intracellular H(2)O(2). Incubation of CHO-K1 cells with ANE (400-800 microg/ml) for 24 hr caused G2/M arrest, and prolonged exposure to ANE (800 microg/ml) significantly induced cell death. Surprisingly, ANE itself caused cytokinesis failure and subsequent increase in binucleated cell formation. Coexposure to catalase (2,000 U/ml) and ANE (800 microg/ml) reduced the generation of binucleated cells, indicating that ANE-induced cytokinesis failure was associated with oxidative stress. Following prolonged exposure to ANE, an accumulation of hyperploid/aneuploid cells concomitant with bi-, micro- or multinucleated cells was found. In summary, our results demonstrate that ANE exposure to CHO-K1 cells caused increased MN frequency, G2/M arrest, cytokinesis failure, and an accumulation of hyperploid/aneuploid cells. These events are associated with an increase in intracellular H(2)O(2) level and actin filament disorganization.
Chiu-Chun Lin; Mei-Chi Chang; Hsiao-Hua Chang; Tong-Mei Wang; Wan-Yu Tseng; Tseng-Fang Tai; Hung-Wei Yeh; Ting-Ting Yang; Liang-Jiunn Hahn; Jiiang-Huei Jeng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  50     ISSN:  1098-2280     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-10     Completed Date:  2009-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  367-74     Citation Subset:  IM    
Department of Dentistry, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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MeSH Terms
Actins / metabolism*
Areca / chemistry*
CHO Cells
Cell Cycle / drug effects
Cell Proliferation / drug effects
Cytokinesis / drug effects*
Hydrogen Peroxide / metabolism
Micronuclei, Chromosome-Defective / chemically induced*
Plant Extracts / chemistry,  toxicity*
Reactive Oxygen Species / metabolism*
Reg. No./Substance:
0/Actins; 0/Plant Extracts; 0/Reactive Oxygen Species; 7722-84-1/Hydrogen Peroxide

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

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