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


Karaman E. F., Ozden S.

MYCOTOXIN RESEARCH, vol.35, no.3, pp.309-320, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 3
  • Publication Date: 2019
  • Doi Number: 10.1007/s12550-019-00358-8
  • Journal Name: MYCOTOXIN RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.309-320
  • Keywords: Zearalenone, DNA methylation, Metabolism-related genes, Nuclear receptor genes, MCF7 cells, MCF10F cells, BREAST-CANCER-CELLS, FATTY-ACID SYNTHASE, ESTROGEN-RECEPTOR-BETA, OXIDATIVE STRESS, EPIGENETIC MODIFICATIONS, FUSARIUM MYCOTOXINS, ADDUCT FORMATION, PROTECTIVE ROLE, DOWN-REGULATION, PPAR-GAMMA
  • Istanbul University Affiliated: Yes

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 24h were found to be 191 mu mol/L and 92.6 mu mol/L in MCF7 cells and 67.4 mu mol/L and 79.5 mu mol/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 PPAR gamma. We suggested that ZEN could alter levels of global DNA methylation and impair metabolism-related pathways.