Related Experiment Video

Updated: Aug 20, 2025

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

3.7K

DON entry into the nucleus induces DNA damage, apoptosis and cycle arrest in GES-1 cells

Silu Hou1, Yuqiang Cheng1, Zhaofei Wang1

  • 1Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|November 25, 2022
PubMed

Insights

Deoxynivalenol (DON), a Fusarium mycotoxin, damages gastric cells by entering the nucleus, causing DNA damage, apoptosis, and cell cycle arrest. It alters redox homeostasis and mitochondrial function without inducing ROS production.

Area of Science:

  • Toxicology
  • Cell Biology
  • Gastroenterology

Background:

  • Deoxynivalenol (DON) is a prevalent mycotoxin from Fusarium species, belonging to trichothecenes.
  • The precise mechanisms of DON toxicity in mammalian cells, particularly in the gastric system, remain unclear.
  • The gastric mucosa serves as the initial defense against ingested toxins, making it a primary target for DON exposure.

Purpose of the Study:

  • To investigate the toxic effects of DON on human gastric mucosal epithelial cells (GES-1).
  • To elucidate the molecular mechanisms underlying DON-induced cytotoxicity in gastric cells.

Main Methods:

  • Exposure of GES-1 cells to DON.
  • Assessment of cell viability, ROS production, and mitochondrial membrane potential.
  • Analysis of ATP levels, DNA damage, and apoptosis markers (p53, Bcl-2 family).
  • Investigation of cell cycle regulation pathways (ATM-chk2-cdc25C, ATM-p53).

Main Results:

  • DON significantly inhibited GES-1 cell activity but did not induce ROS production.
  • Intracellular redox homeostasis was disrupted, mitochondrial membrane potential decreased, and ATP levels increased.
  • DON induced DNA damage, triggering apoptosis via p53 and Bcl-2 family regulation.
  • Activation of ATM-chk2-cdc25C and ATM-p53 pathways led to G2-phase cell cycle arrest.
  • DON entered the nucleus via diffusion and did not directly target mitochondria.

Conclusions:

  • DON induces cytotoxicity in gastric cells by entering the nucleus, causing DNA damage, apoptosis, and cell cycle arrest.
  • These findings provide critical insights into DON's role in gastric disease pathogenesis.
  • The study highlights the complex cellular responses to DON exposure in the gastric epithelium.
Keywords:
ATMApoptosisCycle arrestDNA damageDeoxynivalenolp53

More Related Videos

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry08:21

Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry

Published on: September 1, 2019

13.5K
Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

4.1K

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.5K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.7K
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
3.1K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K