Long-term mucosal injury and repair in a murine model of pelvic radiotherapy

Sci Rep. 2019 Sep 24;9(1):13803. doi: 10.1038/s41598-019-50023-4.

Abstract

Chronic intestinal injury after pelvic radiotherapy affects countless cancer survivors worldwide. A comprehensive understanding of the long-term injury dynamics is prevented in available animal models. With linear accelerators that are used to treat cancer in patients, we irradiated a small volume encompassing the colorectum in mice with four fractions of 8 Gy per fraction. We then determined the long-term dynamics of mucosal injury, repair, and the duration of inflammation. We show that crypt fission, not cell proliferation, is the main long-term mechanism for rescuing crypt density after irradiation, and provides a potentially wide window for clinical interventions. Persisting macrophage aggregations indicate a chronic mucosal inflammation. A better understanding as to how crypt fission is triggered and why it fails to repair fully the mucosa may help restore bowel health after pelvic radiotherapy. Moreover, anti-inflammatory interventions, even if implemented long after completed radiotherapy, could promote bowel health in pelvic cancer survivors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / radiation effects
  • Colon / radiation effects
  • Disease Models, Animal
  • Humans
  • Inflammation / physiopathology
  • Intestinal Mucosa / radiation effects*
  • Macrophages / radiation effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pelvis / radiation effects*
  • Radiotherapy / adverse effects*