DON induced DNA damage triggers absence of p53-mediated G2 arrest and apoptosis in IPEC-1 cells

In this study, we explored the detrimental impacts of DON on porcine intestinal epithelial cells (IPEC-1), serving as a representative model for porcine intestinal epithelial cells. After treating cells with DON for 24 h, DON can significantly inhibit the activity of cells, induce the production of reactive oxygen species (ROS), significantly reduce the content of glutathione and the activity of catalase, and increase the activity of superoxide dismutase and malondialdehyde, leading to an imbalance in intracellular redox status. In addition, DON can induce DNA double-strand breaks, and decrease mitochondrial membrane potential. Furthermore, DON can promote the release of Cyt C through changes in mitochondrial permeability through inhibit the expression of B-cell lymphoma 2 (Bcl-2) proteins, leading to apoptosis through the mitochondrial pathway. On the other hand, we found that DON can cause IPEC-1 cells G2 phase cycle arrest. Different with our pervious study, DON induces cell cycle arrest in the G2 phase only by activating the ATM-Chk2-Cdc 25 C pathway, but cannot regulate the cell cycle arrest via the ATM-p53 pathway. These results indicate that DON can induce the same toxic phenotype in different cells, but its toxic mechanism is different. All these provide a rationale for revealing DON induced cytotoxicity and intestinal diseases.PMID:38104654 | DOI:10.1016/j.tox.2023.153707
Source: Toxicology - Category: Toxicology Authors: Source Type: research