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

Journal article
Authors Dilip Malipatlolla
Piyush Patel
Fei Sjöberg
Sravani Devarakonda
Marie Kalm
Eva Angenete
Elinor Bexe-Lindskog
Rita Grander
Linda Persson
A. Stringer
Ulrica Wilderäng
John Swanpalmer
Hans-Georg Kuhn
Gunnar Steineck
Cecilia Bull
Published in Scientific Reports
Volume 9
ISSN 2045-2322
Publication year 2019
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Surgery
Institute of Clinical Sciences, Department of Oncology
Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Pharmacology
Language en
Keywords radiation-therapy, crypt fission, proliferation, apoptosis, colon, macrophages, growth, cells, Science & Technology - Other Topics
Subject categories Cancer and Oncology


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.

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