Significance of stem cell competition in the dose-rate effects

The system of radiological protection has been functioning well and is sufficiently robust. However, it needs to be further improved by new scientific findings. At low dose and low dose rate, which are the main areas of radiological protection, carcinogenesis is regarded as the main risk and its biological mechanisms need to be elucidated. Biological effect of a given dose generally decreases with a decreasing radiation dose rate, which is known as a ‘dose-rate effect’. Tissue stem cells are considered as targets for radiation-induced carcinogenesis. In tissues exposed to low dose of radiation, non-irradiated cells begin to appear when irradiation doses are approximately lower than the elemental dose. Under heterogeneous exposure conditions, biological effects could be reduced if damaged stem cells are eliminated by ‘stem cell competition’. Here we showed that proliferation of irradiated intestinal stem cells was inhibited by the presence of surrounding non-irradiated stem cells in the intestinal organoid, which is three-dimensional cultured tissue model generated from intestinal stem cells. Additionally, we found that x-ray-microbeam-irradiated stem cell and its daughter cells were excluded from the organoid. These results suggest that stem cell competition would play an important role in suppression of carcinogenesis under very low-dose-rate irradiation condition.