In vitro and in silico insights into moniliformin induced global DNA methylation in liver cells
Abstract
Moniliformin (MON) is a mycotoxin that is not routinely monitored in foods; however, it is increasingly recognized as an emerging food safety concern. Although some clastogenic effects were observed, non-genotoxic mechanisms may also contribute to the toxic effects of MON. Therefore, this study aims to investigate the effects of global DNA methylation, the most studied non-genotoxic mechanism, on MON toxicity in human hepatocarcinoma (HepG2) cells. HepG2 cells were exposed to MON at 5, 10, and 50 M concentrations for 24 hours. Global DNA methylation levels and gene expression of DNMT1, DNMT3A, DNMT3B, TET1, TET2, and TET3 were analyzed. Interactions among B-DNA, DNMT1, DNMT3A, DNMT3B, and MON were investigated using molecular docking. MTT cytotoxicity assay revealed that the IC50 value of MON in HepG2 cells was 253±8.41 M. MON at 10 and 50 μM resulted in at least a 2.18-fold increase (P<0.05) in global DNA methylation levels, accompanied by upregulated expression of DNMT1 and DNMT3A. Moreover, 5, 10, and 50 M of MON resulted in at least 2.37-fold (P<0.05) increase in TET1 genes. In contrast, TET2 expression was significantly downregulated by at least 37% (P<0.05) and 42% (P<0.05) at 10 and 50 M of MON. However, TET3 expression showed no significant change in any treatment group. MON formed hydrogen bonds with B-DNA, DNMT1, DNMT3A, and DNMT3B. However, the binding energy calculations indicate that the interactions are not biologically active. This study suggests that alterations in global DNA methylation might have a role in MON-induced toxicity.
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References
- Ahmadnejad M, Amirizadeh N, Mehrasa R, et al (2017): Elevated expression of DNMT1 is associated with increased expansion and proliferation of hematopoietic stem cells co-cultured with human MSCs. Blood Res, 52, 25.
- Alrehaili AA, Gharib AF, Alghamdi SA, et al. (2023): Evaluation of TET family gene expression and 5-hydroxymethylcytosine as potential epigenetic markers in non-small cell lung cancer. In Vivo, 37, 445-453.
- Anteneh H, Fang J, Song J (2020): Structural basis for impairment of DNA methylation by the DNMT3A R882H mutation. Nat Commun, 11, 2294.
- Bertuzzi T, Giorni P, Rastelli S, et al (2020): Co-occurrence of moniliformin and regulated Fusarium toxins in maize and wheat grown in Italy. Molecules, 25, 2440.
- Bioinformatics RCSB. RCSB Protein Data Bank: RCSB PDB; 2025. Available from: https://www.rcsb.org/. (Accessed May 25, 2005).
- Broomhead J, Ledoux D, Bermudez A, et al (2002): Chronic effects of moniliformin in broilers and turkeys fed dietary treatments to market age. Avian Dis, 46, 901-908.
- Cakir MC, Ozden S (2025): The role of global DNA methylation in citrinin induced toxicity: in vitro and in silico approach. Toxicol Rep, 102046.
- Çetin Y, Bullerman LB (2005): Cytotoxicity of Fusarium mycotoxins to mammalian cell cultures as determined by the MTT bioassay. Food Chem Toxicol, 43, 755-764.
Details
Primary Language
English
Subjects
Veterinary Mycology
Journal Section
Research Article
Authors
Zeynep Ciftci
0000-0001-5349-8103
Türkiye
Zeynep Rana Güler
0000-0003-0817-4315
Türkiye
Metin Caner Çakır
0009-0005-5471-6148
Türkiye
Sibel Özden
*
0000-0002-1662-2504
Türkiye
Early Pub Date
December 2, 2025
Publication Date
April 1, 2026
Submission Date
July 2, 2025
Acceptance Date
November 20, 2025
Published in Issue
Year 2026 Volume: 73 Number: 2