Alterations in global DNA methylation and metabolism-related genes caused by zearalenone in MCF7 and MCF10F cells

AbstractZearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced byFusarium fungi. ZEN has endocrine disruptor effects and could impair the hormonal balance. Here, we aimed at investigating possible effects of ZEN on metabolism-related pathways and its relation to epigenetic mechanisms in breast adenocarcinoma (MCF7) and breast epithelial (MCF10F) cells. Using the MTT and neutral red uptake (NRU) cell viability tests, IC50 values of ZEN after 24  h were found to be 191 μmol/L and 92.6 μmol/L in MCF7 cells and 67.4 μmol/L and 79.5 μmol/L in MCF10F cells. A significant increase on global levels of 5-methylcytosine (5-mC%) was observed for MCF7 cells, correlating with the increased expression of DNA methyltransferases. No alterations were observed on levels of 5-mC% and expression of DNA methyltransferases for MCF10F cells. Further, at least threefold upregulation compared to control was observed for several genes related to nuclear receptors and metabolism in MCF7 cells, while some of these genes were downregulated in MCF10F ce lls. The most notably altered genes wereIGF1,HK2,PXR, andPPAR γ. We suggested that ZEN could alter levels of global DNA methylation and impair metabolism-related pathways.
Source: Mycotoxin Research - Category: Toxicology Source Type: research