Alteration on global and gene-spesific DNA methylation and global histone modifications in HepG2 cells in response to BPA

Authors : Mine Şenyıldız, Ecem Fatma Karaman, Serap Sancar Baş, Pelin Arda Pirinççi, Sibel Özden

Pages : 97-114

View : 39 | Download : 9

Publication Date : 2016-12-26

Article Type : Research Paper

Abstract :Bisphenol A insert ignore into journalissuearticles values(BPA);, as synthetic monomer used in industry in the  production of polycarbonate plastic and epoxy resins, has endocrine disruptor  properties and high risk on human health. Continuous release of free BPA into  food, beverages, and the environment has resulted in a widespread human exposure  to this chemical. Recent studies have showed the role of endocrine effects of  environmental chemicals on the changes in gene expression may be associated  with epigenetic mechanisms such as DNA methylation and histone modifications.  The aim of the study was to investigate dose-related effects of BPA insert ignore into journalissuearticles values(0, 0.1 μM,  1 and 10 mM for 48 and 96 h); on global and gene-spesific insert ignore into journalissuearticles values(p16, cyclin D2 and  Rassf1 genes); DNA methylation in human hepatocarcinoma insert ignore into journalissuearticles values(HepG2); cells.  We also investigated global histone modifications such as H3K9 trimethylation  insert ignore into journalissuearticles values(H3K9me3);, H3K9 acetylation insert ignore into journalissuearticles values(H3K9ac);, H3K27 trimethylation insert ignore into journalissuearticles values(H3K27me3);.  The 50% inhibitory concentration insert ignore into journalissuearticles values(IC50); value of BPA was determined as 134 and  180 μM in HepG2 cells for 24 h by MTT and neutral red uptake insert ignore into journalissuearticles values(NRU); tests,  respectively. We observed decrease on the global levels of 5-methylcytosine and  5-hydroxymethylcytosine at 1 and 10 mM after 96 h BPA exposure. There is no  significant alterations on the promoter-region of methylation and expression of  p16, cyclin D2 and Rassf1 genes. Global levels of H3K9me3 decreased after 0.1  and 1 μM concentration of BPA exposure for 48 h, while increased after 96 h 0.1  and 1 μM of BPA exposure for. Hovewer, it has not been observed significantly  changes for the global levels of H3K27me3 and H3K9ac. In this study we suggest  that BPA may disrupt epigenetic events by altering global and gene-spesific DNA  methylation and histone modifications in HepG2 cells.
Keywords : Bisphenol A, DNA methylation, cytotoxicity, histone modifications, HepG2 cells

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