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

• Published in: International journal of molecular sciences 2024-09, Vol.25 (18), p.10129
• Main Authors: Fischer, Franziska, Stößer, Sandra, Wegmann, Lisa, Veh, Eva, Lumpp, Tatjana, Parsdorfer, Marlene, Schumacher, Paul, Hartwig, Andrea
• Format: Article
• Language: English
• Subjects: A549 Cells; Cell cycle; chromate; Chromates; Chromates - toxicity; Cytotoxicity; DNA damage; DNA Damage - drug effects; DNA methylation; DNA Methylation - drug effects; Environmental aspects; Epigenesis, Genetic - drug effects; epigenetic; Epigenetic inheritance; Epigenetics; Gene expression; gene expression profiles; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Health aspects; Humans; Ligands; long-term exposure; Lung cancer; Lung cancer, Non-small cell; oxidative stress; Risk factors; Transcription factors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251810129

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. Taken together, the results suggest specific differences in toxicity profiles when comparing short-term and long-term exposure to chromate in A549 cells.