Modeling Radiation-Induced Epithelial Cell Injury in Murine Three-Dimensional Esophageal Organoids

Area of Science:

• Oncology
• Radiation Biology
• Gastroenterology

Background:

• Esophageal squamous cell carcinoma (ESCC) is a severe outcome of esophageal radiation exposure.
• Understanding radiation's impact on esophageal epithelium is crucial for assessing ESCC risk.
• Radiation quality and dose significantly influence cellular responses and long-term effects.

Purpose of the Study:

• To investigate esophageal epithelial radiosensitivity and its link to ESCC risk.
• To explore dose- and radiation quality-dependent changes in esophageal epithelium.
• To analyze the role of stress pathways and differentiation in radiation-induced esophageal injury.

Main Methods:

• Utilized a murine three-dimensional (3D) organoid model of esophageal epithelium.
• Exposed organoids to different doses and qualities of radiation (Fe ions vs. Cs).
• Assessed changes in squamous differentiation, DNA damage foci (53BP1), and MAPK/SAPK stress pathway signaling.

Main Results:

• High-LET Fe ion exposure caused more persistent changes in differentiation and DNA damage than Cs.
• Similar MAPK/SAPK pathway alterations were observed for both radiation types.
• Low-dose (0.1 Gy) high-LET radiation induced significant morphological changes, suggesting a bystander effect.
• Persistent stress signaling was observed even at low doses, impacting epithelial differentiation.

Conclusions:

• Low-dose radiation exposure can induce persistent stress responses in esophageal epithelium.
• Radiation quality and dose influence the severity and persistence of cellular alterations.
• These findings offer insights into the pathogenesis of radiation-induced esophageal injury and early carcinogenesis.