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Original Articles

Cytotoxic Effects Produced by Arecoline Correlated to Epigenetic Regulation in Human K-562 Cells

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Pages 737-745 | Received 15 Aug 2010, Accepted 08 Sep 2010, Published online: 08 Apr 2011
 

Abstract

Epigenetic effects are considered heritable but may also be modified by environmental factors. Arecoline (ARC), a major component of areca nut alkaloids, is an important environmental risk factor for oral cancer and hepatocellular carcinomain Taiwan. The aim of this study was to determine the influence of ARC on the epigenome. The mRNA expression of histone methyltransferases, acetyltransferases, and demethylases were assessed in K-562 cells following exposure to ARC. Results demonstrated that ARC produced changes in the expressions of several genes catalyzing histone methylation (Mll, Setdb1, and Suv39h2), acetylation (Atf2), and demethylation (JMJD6). Since H3K9 methylation is involved in maintaining the stability of heterochromatin structures and inactivating euchromatic gene expressions, data suggest that the ARC-induced epigenetic changes play a role in the mechanisms underlying chemical-mediated cytotoxicity and genotoxicity.

Acknowledgments

This study was supported by grants from the Center for Excellence in Environmental Medicine, Kaohsiung Medical University (U1-9709 and U1-9809) and the Kaohsiung Medical University Hospital (98-G-7-52).

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