Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing

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 tamoxifendependent 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-creert2 × 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.