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. 2019 Sep 24;9:13803. doi: 10.1038/s41598-019-50023-4

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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(a) Numbers of crypt fission events per 6 circumferences after different fractionation schedules. The occurrence of crypt fission is dose-dependent, as seen 6 weeks after irradiation. (b) Number of crypt fission events per six circumferences at 24 hours, and at 1 week, 6 weeks, 18 weeks, and 30 weeks after irradiation or sham-irradiation. A few of the irradiated animals show many crypt fission events 1 week after irradiation, and at 6 weeks post-irradiation all the animals exhibit crypt fission; thereafter the number of fission events declines. At 30 weeks post-irradiation, there is no difference in the number of crypt fissions between the irradiated and sham-irradiated animals. (c) Irradiated mouse colorectal mucosa 6 weeks after 8 Gy × 4 of irradiation. The dark nuclei are cells that are labelled with BrdU, showing newly born cells migrating to form two new crypt walls at the crypt mid-line (arrow). (d) Crypt fission in a non-irradiated human rectal biopsy (arrow), showing multiple darkly stained Ki-67⁺ proliferating cells at the bottom of the dividing crypt. (e) Crypt fission in a human rectal biopsy (arrow) harvested 11 weeks after 1.8 Gy × 25. A few Ki-67⁺ proliferating cells are seen at the bottom of one of the two resulting crypts.