Alteration in global DNA methylation after bisphenol a exposure in MCF-7 cells

Abstract

Abstract: Bisphenol A (BPA), as synthetic monomer used especially 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 environment has resulted in a widespread human exposure to this chemical. Role of endocrine effects of environmental chemicals such as BPA on the changes in gene expression may be associated with epigenetic mechanisms. Early detection of aberrant DNA methylation, which regulates transcription of tumor suppressor genes and activation of oncogenes in carcinogenesis process, may provide powerful mechanistic insights in the toxicity of BPA. 5-hydroxymethylcytosine (5-hmC), oxidation product of 5-methylcytosine (5-mC), is considered as a new epigenetic DNA modification with relevant roles in cell homeostasis regulating DNA demethylation and transcription. Our aim was to investigate possible changes in the global 5-mC and 5-hmC after 48 and 96 h BPA exposure in mammalian breast cancer cell line (MCF-7). 50% of inhibitory concentration (IC50) value of BPA was determined as 148 μM by MTT cytotoxicity test in MCF-7 cells. We revealed decrease on the level of global 5-mC after BPA exposure (100 nM and 1 μM) for 48 and 96 h by using 5-mC Elisa kit, whereas non-significant slightly increase were observed in the levels of 5-hmC%. We suggested that global DNA methylation may be involved in BPA toxicity in breast cancer cells. Furthermore, evaluation on the expression of enzymes involved in DNA methylation and demethylation after BPA exposure should be investigated in cell cultures. Key words: Bisphenol A, 5-methylcytosine, 5-hydroxymethylcytosine, Cytotoxicity, MCF-7 cells.