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Updated: Aug 21, 2026
Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
Effect of reduced EGFR function on the radiosensitivity and proliferative capacity of mouse jejunal crypt clonogens
Radhika Iyer1, Howard D Thames, Ja Rhonda Tealer
1Department of Biological Sciences, Ohio University, Athens, OH, USA.
Background And Purpose:
Previous data indicate that the EGFR pathway is involved in the response of tumor cell lines to irradiation. To determine if this receptor plays a role in the response of the intestinal mucosa, the effect of a spontaneous mutation in EGFR (B6C3-a-wa-2) on radiosensitivity and proliferative capacity was investigated using in vivo clonogenic assays and immunohistochemistry.
Patients And Methods:
EGFR mutant mice were compared with wild-type mice using the in vivo jejunal microcolony assay using single and split doses to measure the radiosensitivity and repopulation of clonogenic jejunal mucosal cells. In addition, paraffin-embedded tissue sections were assessed for proliferation (PCNA), DNA repair (Ku70 and gamma H2AX), and apoptosis (TUNEL) by immunofluorescent staining (wild-type vs. heterozygous only) at various times after 5 Gy single dose.
Results:
After the high doses used in the split-dose experiments, EGFR heterozygous and homozygous mutant mice were significantly more radiosensitive than their wild-type littermates. There was no clear difference in split-dose repair based on EGFR function. After 5 Gy single dose there were significantly more apoptotic cells within the crypts of heterozygous mice than of wild-type mice, beginning at 3h post irradiation. Decreased proliferation was observed only in the homozygous mutant mice. PCNA staining was lower in the heterozygous mice than in wild-type mice at 1 and 3 h post-5 Gy.
Conclusion:
The results indicate that after high doses the radiosensitivity of EGFR mutant mice is significantly higher than that of wild-type, and that this could be the result of an increase in apoptosis rather than reduced DNA repair. Proliferative capacity was modestly reduced, but only in the homozygous mutants.
Insights
Mice with mutations in the Epidermal Growth Factor Receptor (EGFR) show increased radiosensitivity in their intestinal lining, primarily due to higher rates of apoptosis, not impaired DNA repair. Proliferation was only affected in homozygous mutants.
Area of Science:
- Oncology
- Gastroenterology
- Radiation Biology
Background:
- The Epidermal Growth Factor Receptor (EGFR) pathway is implicated in tumor cell responses to irradiation.
- Its role in intestinal mucosa radiosensitivity requires further investigation.
Purpose of the Study:
- To investigate the effect of EGFR mutations on intestinal mucosa radiosensitivity and proliferative capacity in vivo.
- To compare EGFR mutant mice with wild-type mice.
Main Methods:
- In vivo jejunal microcolony assay to measure radiosensitivity and repopulation.
- Immunohistochemistry to assess proliferation (PCNA), DNA repair (Ku70, gamma H2AX), and apoptosis (TUNEL).
Main Results:
- EGFR mutant mice (heterozygous and homozygous) exhibited significantly higher radiosensitivity than wild-type mice after high doses.
- Increased apoptosis was observed in heterozygous mutants post-irradiation, suggesting apoptosis as a key factor.
- Reduced proliferation was noted only in homozygous mutant mice.
Conclusions:
- EGFR mutant mice demonstrate heightened radiosensitivity, likely due to increased apoptosis rather than compromised DNA repair.
- The proliferative capacity of the intestinal mucosa is modestly reduced in homozygous EGFR mutants.
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