Lin C.-C.Chang M.-C.HSIAO-HUA CHANGTONG-MEI WANGWAN-YU TSENGTai T.-F.Yeh H.-W.Yang T.-T.Hahn L.-J.JIIANG-HUEI JENG2021-07-052021-07-0520090893-6692https://www.scopus.com/inward/record.uri?eid=2-s2.0-67549089996&doi=10.1002%2fem.20463&partnerID=40&md5=102dd7b79fcf70ec54949bdfe9afea32https://scholars.lib.ntu.edu.tw/handle/123456789/569446Epidemiological 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 H2O2. Incubation of CHO-K1 cells with ANE (400-800 lg/ml) for 24 hr caused G2/M arrest, and prolonged exposure to ANE (800 lg/ 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 lg/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 H2O2 level and actin filament disorganization. ? 2009 Wiley-Liss, Inc.[SDGs]SDG3catalase; reactive oxygen metabolite; actin; hydrogen peroxide; plant extract; actin filament; aneuploidy; animal cell; article; betel nut; cell death; cytokinesis; genotoxicity; micronucleus; nonhuman; ovary cell; oxidative stress; animal; betel nut; cell cycle; cell proliferation; chemically induced disorder; chemistry; CHO cell; Cricetulus; cytokinesis; drug effect; hamster; metabolism; micronucleus; Areca catechu; Cricetulus griseus; Piper betel; Actins; Animals; Areca; Cell Cycle; Cell Proliferation; CHO Cells; Cricetinae; Cricetulus; Cytokinesis; Hydrogen Peroxide; Micronuclei, Chromosome-Defective; Plant Extracts; Reactive Oxygen Speciesjournal article10.1002/em.20463191979892-s2.0-67549089996