2. Academic Validation
  3. DON induced DNA damage triggers absence of p53-mediated G2 arrest and apoptosis in IPEC-1 cells

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

  • Toxicology. 2023 Dec 15:153707. doi: 10.1016/j.tox.2023.153707.
Silu Hou 1,  Jingjiao Ma 2,  Yuqiang Cheng 2,  Zhaofei Wang 2,  Guiping Wang 3,  Aiqing Jia 3,  Hengan Wang 2,  Jianhe Sun 2,  Yaxian Yan 4
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai 200240, China; State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Demonstration Center of Food Quality and Safety Testing Technology, Tianjin University of Science and Technology, Tianjin 300457, China.
  • 2 Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai 200240, China.
  • 3 Guangdong Haid Group Co. Limited., Guangzhou Guangdong 511400.
  • 4 Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai 200240, China. Electronic address: yanyaxian@sjtu.edu.cn.
PMID: 38104654 DOI: 10.1016/j.tox.2023.153707
Abstract

Deoxynivalenol (DON) stands among the prevalent mycotoxins, and usually contaminates cereal foods and animal feed, leading to human and animal clinical poisoning symptoms such as abdominal pain, diarrhea, and vomiting. To date, the mechanism of toxicity of DON in different mammalian cells is not fully elucidated. 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 24hours, 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 25C 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.

Keywords

ATM-Chk2-Cdc25C; Apoptosis; Deoxynivalenol; G2 arrest; IPEC-1cell.

Figures
Products