title: Cytotoxic effects produced by arecoline correlated to epigenetic regulation in human K-562 cells.
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.
authors.affiliation: Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Lin
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Chang
authors.forename: Yung-Hsiu
authors.initials: YH
authors.lastname: Chen
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Lee
authors.forename: Yi-Hsiung
authors.initials: YH
authors.lastname: Lin
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
mesh_terms: D001115:Arecoline / Q000633:toxicity*; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010936:Plant Extracts / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D003603:Cytotoxins; D006657:Histones; D010936:Plant Extracts; D012333:RNA, Messenger; D001115:Arecoline; D056466:Histone Demethylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases