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标题：Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing
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作者：Kensuke Otsuka ; Toshiyasu Iwasaki
期刊名称：Journal of Radiation Research
印刷版ISSN：0449-3060
电子版ISSN：1349-9157
出版年度：2015
卷号：56
期号：4
页码：615-622
DOI：10.1093/jrr/rrv012
摘要：An understanding of the dynamics of intestinal Lgr5( ) stem cells is important for elucidating the mechanism of colonic cancer development. We previously established a method for evaluating Lgr5( ) stem cells by tamoxifen-dependent Lgr5-lineage tracing and showed that high-dose-rate radiation stimulated replenishment of colonic stem cells. In this study, we evaluated the effects of low-dose-rate radiation on stem cell maintenance. Tamoxifen (4OHT)-injected Lgr5-EGFP-IRES-Cre(ERT2) × ROSA-LSL-LacZ mice were used, LacZ-labeled colonic crypts were enumerated, and the loss of LacZ( ) crypts under low-dose-rate radiation was estimated. After 4OHT treatment, the number of LacZ-labeled Lgr5( ) stem cells was higher in the colon of infant mice than in adult mice. The percentage of LacZ-labeled crypts in infant mice rapidly decreased after 4OHT treatment. However, the percentage of labeled crypts plateaued at ∼2% at 4 weeks post-treatment and remained unchanged for up to 7 months. Thus, it will be advantageous to evaluate the long-term effects of low-dose-rate radiation. Next, we determined the percentages of LacZ-labeled crypts irradiated with 1 Gy administered at different dose rates. As reported in our previous study, mice exposed to high-dose-rate radiation (30 Gy/h) showed a marked replenishment (P = 0.04). However, mice exposed to low-dose-rate radiation (0.003 Gy/h) did not exhibit accelerated stem-cell replenishment (P = 0.47). These findings suggest the percentage of labeled crypts can serve as a useful indicator of the effects of dose rate on the stem cell pool. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.
关键词：Lgr5;dose-rate effects;low-dose rate;tissue stem cell