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Chromate Affects Gene Expression and DNA Methylation in Long-Term In Vitro Experiments in A549 Cells

Fischer, Franziska Stephanie 1; Stößer, Sandra 1; Wegmann, Lisa 1; Veh, Eva 1; Lumpp, Tatjana 1; Parsdorfer, Marlene 1; Schumacher, Paul 1; Hartwig, Andrea 1
1 Institut für Angewandte Biowissenschaften (IAB), Karlsruher Institut für Technologie (KIT)

Abstract:

Chromate has been shown to dysregulate epigenetic mechanisms such as DNA methylation, leading to changes in gene expression and genomic instability. However, most in vitro studies are limited to short incubation periods, although chronic exposure may be more relevant for both environmental and occupational exposure. In this study, human adenocarcinoma A549 cells were treated with 1, 2 or 5 µM chromate for 24 h and compared with incubations with 0.2, 0.5 or 1 µM chromate for 1 to 5 weeks. Chromium accumulated in a pronounced time- and concentration-dependent manner after short-term treatment, whereas a plateau of intracellular chromium content was observed after long-term treatment. While short-term treatment induced a G2 arrest of the cell cycle, this effect was not observed after long-term treatment at lower concentrations. The opposite was observed for global DNA methylation: while short-term treatment showed no effect of chromate, significant dose-dependent hypomethylation was observed in the long-term experiments. Time-dependent effects were also observed in a high-throughput RT-qPCR gene expression analysis, particularly in genes related to the inflammatory response and DNA damage response. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000175074
Veröffentlicht am 18.10.2024
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 20.09.2024
Sprache Englisch
Identifikator ISSN: 1661-6596, 1422-0067
KITopen-ID: 1000175074
Erschienen in International Journal of Molecular Sciences
Verlag MDPI
Band 25
Heft 18
Seiten 10129
Schlagwörter chromate, epigenetic, DNA methylation, long-term exposure, gene expression profiles, oxidative stress, DNA damage response, inflammation
Nachgewiesen in Scopus
Web of Science
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