Abstract
Radiation-induced cancer mortality is presumed to be proportional to the dose of ionizing radiation, but it remains unclear whether the radiation-induced DNA damage and gene mutations accumulate in the tissue stem cells, putative targets of carcinogenesis. To elucidate the mechanism of the stem cell turnover, we used the lineage tagging system of Lgr5-cre/Rosa-lacZ mice to determine the kinetics of stem cell competition after ionizing radiation exposure.
In this study, we found that the efficacy of tamoxifen (4OHT) in lineage tagging induction is different between small intestine and colon, and by the age of induction. Furthermore, a frequency of tagged crypts gradually decreased after 4OHT treatment. These results demonstrate that the dynamics of tagged crypt is regulated by both of the recombination frequency and monoclonal conversion in each crypt. Using this experimental model, we exposed 4 Gy of X-rays to the mice after 4OHT treatment and found that the frequency of tagged-crypts immediately decreases after irradiation. These results indicate that ionizing radiation may accelerate the turnover rate of intestinal stem cells.
