Different bisphenols induce non-monotonous changes in miRNA expression and LINE-1 methylation in two cell lines

Autor(en)
Julia Oldenburg, Maria Fürhacker, Christina Hartmann, Alexander Haslberger
Abstrakt

4,4'-Isopropylidenediphenol (bisphenol A, BPA), a chemical substance that is widely used mainly as a monomer in the production of polycarbonates, in epoxy resins, and in thermal papers, is suspected to cause epigenetic modifications with potentially toxic consequences. Due to its negative health effects, BPA is banned in several products and is replaced by other bisphenols such as bisphenol S and bisphenol F. The present study examined the effects of BPA, bisphenol S, bisphenol F, p,p'-oxybisphenol, and the BPA metabolite BPA beta-D-glucuronide on the expression of a set of microRNAs (miRNAs) as well as long interspersed nuclear element-1 methylation in human lung fibroblast and Caco-2 cells. The results demonstrated a significant modulation of the expression of different miRNAs in both cell lines including miR-24, miR-155, miR-21, and miR-146a, known for their regulatory functions of cell cycle, metabolism, and inflammation. At concentrations between 0.001 and 10 mu g/ml, especially the data of miR-155 and miR-24 displayed non-monotonous and often significant dose-response curves that were U- or bell-shaped for different substances. Additionally, BPA beta-D-glucuronide also exerted significant changes in the miRNA expression. miRNA prediction analysis indicated effects on multiple molecular pathways with relevance for toxicity. Besides, long interspersed nuclear element-1 methylation, a marker for the global DNA methylation status, was significantly modulated by two concentrations of BPA and p,p'-oxybisphenol. This pilot study suggests that various bisphenols, including BPA beta-D-glucuronide, affect epigenetic mechanisms, especially miRNAs. These results should stimulate extended toxicological studies of multiple bisphenols and a potential use of miRNAs as markers.

Organisation(en)
Department für Ernährungswissenschaften
Externe Organisation(en)
Universität für Bodenkultur Wien, Umweltbundesamt
Journal
Environmental Epigenetics
Band
7
Anzahl der Seiten
10
DOI
https://doi.org/10.1093/eep/dvab011
Publikationsdatum
2021
Peer-reviewed
Ja
ÖFOS 2012
303033 Umweltmedizin
Schlagwörter
Link zum Portal
https://ucris.univie.ac.at/portal/de/publications/different-bisphenols-induce-nonmonotonous-changes-in-mirna-expression-and-line1-methylation-in-two-cell-lines(7209d5ff-1d42-47b2-bbd2-3b9e35f61011).html