title: Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing.
abstract: 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.
authors.affiliation: Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), 2-11-1 Iwado-kita, Komae, Tokyo 201-8511, Japan ohken@criepi.denken.or.jp.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Otsuka
authors.affiliation: Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), 2-11-1 Iwado-kita, Komae, Tokyo 201-8511, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology / Q000528:radiation effects*; D003106:Colon / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D011829:Radiation Dosage; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects
chemical_list: C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled
keywords: Lgr5; dose-rate effects; low-dose rate; tissue stem cell
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