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

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Abstract

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium 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 cells. The most notably altered genes were IGF1, HK2, PXR, and PPARγ. We suggested that ZEN could alter levels of global DNA methylation and impair metabolism-related pathways.

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Abbreviations

5-mC:

5-Methylcytosine

AhR:

Aryl hydrocarbon receptor

Caco-2:

Human colorectal adenocarcinoma cell line

CHO-K1:

Chinese hamster ovary cell line

DNMT1:

DNA methyltransferase 1

ERα:

Estrogen receptor alpha

ERβ:

Estrogen receptor beta

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GLUT2:

Glucose transporter 2

HK2:

Hexokinase 2

IC50 :

50% of inhibitory concentration

IGF1:

Insulin-like growth factor 1

L-FABP:

Liver fatty acid-binding protein

MCF7:

Human breast adenocarcinoma cell line

MCF10F:

Human breast epithelial cell line

MGMT:

O6-Methylguanine-DNA methyltransferase

MTT:

[3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide, a tetrazole]

NRU:

Neutral red uptake

PPARɣ:

Peroxisome proliferator-activated receptor gamma

PXR:

Pregnane X receptor

SH-SY5Y:

Human neuroblastoma cell line

SREBP1c:

Sterol regulatory element-binding protein 1

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Acknowledgements

This work was supported in part by the TUBITAK (2211-C/2015-2 grant for E.F.K.) and Scientific Research Projects Coordination Unit of Istanbul University (project no. TOA-2016-20307).

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  1. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116-Beyazit, Istanbul, Turkey

    Ecem Fatma Karaman & Sibel Ozden

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  1. Ecem Fatma Karaman
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Correspondence to Sibel Ozden.

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Karaman, E.F., Ozden, S. Alterations in global DNA methylation and metabolism-related genes caused by zearalenone in MCF7 and MCF10F cells. Mycotoxin Res 35, 309–320 (2019). https://doi.org/10.1007/s12550-019-00358-8

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