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

ASJC Scopus Sachgebiete

Genetics(clinical), Genetics, Molecular Biology, Health, Toxicology and Mutagenesis

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