Long-term Mucosal Injury and Repair in a Murine Model of Pelvic Radiotherapy

Overview

Journal Sci Rep

Specialty Science

Date 2019 Sep 26

PMID 31551503

Citations 10

Authors

Dilip K Malipatlolla

Piyush Patel

Fei Sjoberg

Sravani Devarakonda

Marie Kalm

Eva Angenete

Elinor Bexe Lindskog

Rita Grander

Linda Persson

Andrea Stringer

Ulrica Wilderang

John Swanpalmer

Hans Georg Kuhn

Gunnar Steineck

Cecilia Bull

Affiliations

Soon will be listed here.

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.

Citing Articles

Metabolic regulation of intestinal homeostasis: molecular and cellular mechanisms and diseases.

Zhang R, Perekatt A, Chen L MedComm (2020). 2024; 5(11):e776.

PMID: 39465140 PMC: 11502721. DOI: 10.1002/mco2.776.

Acute Impacts of Ionizing Radiation Exposure on the Gastrointestinal Tract and Gut Microbiome in Mice.

Jameus A, Dougherty J, Narendrula R, Levert D, Valiquette M, Pirkkanen J Int J Mol Sci. 2024; 25(6).

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Remarkable effects of infliximab on severe radiation-induced side effects in a patient with uterine cervical cancer: a case report.

Moren A, Bull C, Bergmark K J Int Med Res. 2023; 51(12):3000605231208596.

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Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease.

Vitali R, Palone F, De Stefano I, Fiorente C, Novelli F, Pasquali E Int J Mol Sci. 2023; 24(10).

PMID: 37240150 PMC: 10218716. DOI: 10.3390/ijms24108800.

Fibroblast-derived EGF ligand neuregulin 1 induces fetal-like reprogramming of the intestinal epithelium without supporting tumorigenic growth.

Lemmetyinen T, Viitala E, Wartiovaara L, Kaprio T, Hagstrom J, Haglund C Dis Model Mech. 2023; 16(4).

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