2019
DOI: 10.1038/s41598-019-50023-4
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Long-term mucosal injury and repair in a murine model of pelvic radiotherapy

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 cel… Show more

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Cited by 15 publications
(15 citation statements)
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“…The macrophages were seen aggregating in close proximity to vessels and degenerated crypts, creating an inflammatory milieu and perhaps contributing to an abnormal division of crypts (crypt fission) and hindering tissue regeneration for weeks after RT. Similar observations were made within intestinal biopsies from cancer patients after RT and in other preclinical models 16,88 .…”
Section: Immune Mechanisms Of Rt-induced Gut Injurysupporting
confidence: 80%
See 1 more Smart Citation
“…The macrophages were seen aggregating in close proximity to vessels and degenerated crypts, creating an inflammatory milieu and perhaps contributing to an abnormal division of crypts (crypt fission) and hindering tissue regeneration for weeks after RT. Similar observations were made within intestinal biopsies from cancer patients after RT and in other preclinical models 16,88 .…”
Section: Immune Mechanisms Of Rt-induced Gut Injurysupporting
confidence: 80%
“…The intestine is extremely susceptible to acute RT-induced injury, due at least in part to the high proliferation rate of intestinal epithelial cells lining the gut. The high turnover of these cells allows for recovery within weeks 87,88 . However, it is possible that the extent of the injury and repeated fractions of RT might prolong or interrupt the repair process 86 and allow the leakage of the lumen content and the microbiota into the underlying intestinal tissue, which can induce inflammation to promote both acute and chronic damage 16,89 .…”
Section: Immune Mechanisms Of Rt-induced Gut Injurymentioning
confidence: 99%
“…Thus, high-energy photons can be delivered to a highly defined area, thereby avoiding undesirable irradiation of non-target organs. Our previous study showed that irradiation with 8 Gy × 4 fractions was best suited for our model as it inflicted similar pathologic changes in the mouse intestinal mucosa, notably crypt degeneration, as seen in a cancer survivor’s intestinal mucosa irradiated at the pelvic region [ 41 , 42 ]. Furthermore, these mice appear to maintain their overall health and a normal lifespan despite having received high doses of irradiation.…”
Section: Discussionmentioning
confidence: 99%
“…Although we cannot completely rule out the possibility that crypt degeneration peaked earlier than one week for the fiber-consuming group, we have previously shown that crypt degeneration is not immediate after four fractions of 8 Gy. We found very few degenerating crypts 24 h after irradiation in animals consuming a standard chow diet containing 13 percent dietary fiber [ 24 ]. A considerable amount of crypt degeneration was instead found at one week post-irradiation [ 24 ], similar to the peak seen in the animals fed the no-fiber diet.…”
Section: Discussionmentioning
confidence: 99%