The role of global DNA methylation in citrinin induced toxicity: In vitro and in silico approach.

Citrinin (CIT) is a widely occurring mycotoxin which exhibits a variety of toxic effects. Only a few countries have legal limitations on CIT content in foods, despite the dangers it presents. The aim of this study is to investigate the effects of CIT on DNA methylation in SH-SY5Y and HK-2 cells and to perform docking studies to explore the possible interactions between CIT and DNMT enzymes. In SH-SY5Y cells, global DNA methylation levels increased by 1.90-fold (p < 0.05) and 1.50-fold (p < 0.05) at 50 and 100 μM of CIT, respectively. In HK-2 cells, the increase was 3.17-fold (p < 0.05) following exposure to 50 μM of CIT. In SH-SY5Y cells, DNMT-1, DNMT-3a, DNMT-3b and TET-3 expressions increased significantly, while TET-1 and TET-2 expressions decreased significantly. In HK-2 cells, no significant change in DNMT-1 expression was observed, while DNMT-3a and DNMT-3b expressions increased significantly. Significant decreases in TET-1, TET-2 and TET-3 expressions were observed in HK-2 cells. The docking results suggest that CIT may interact with DNMTs with a high degree of binding, which could potentially lead to the inhibition of these enzymes. The results of this study indicate that DNA methylation may be involved in CIT-induced toxicity. Epigenetic mechanisms and in silico studies hold great potential for advancing chemical risk assessment by uncovering toxicity mechanisms, and the standardization of these techniques is crucial for their integration into policymaking. Accordingly, this study introduces a novel aspect of the potential mechanism of CIT in the risk assessment process.