Speaker
Dr
Nobuyuki Hamada
(Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Tokyo 201-8511, Japan)
Description
Ionizing radiation is a well-known carcinogen, but the cell of origin (target cells) is still unidentified for radiation carcinogenesis. Whatever the nature of target cells, the irradiated tissue may accumulate radiation damage causing cancer, if the damaged target cells are not excluded from the tissue through its cell death or tissue turnover. The identification of target cells hence requires a model system that can chase the fate of cells responding to radiation and their descendants within the tissue. For this aim, we have started to set up such system. Among various radiation-responsive genes, p21 (Cdkn1a) was chosen to mark the promoter-activated cells in response to radiation, considering its high signal-to-noise ratio in many tissues. The targeting construct was designed to express CreERT2 (bacteriophage P1-derived Cre recombinase fused to a mutated ligand-binding domain of the human estrogen receptor) in the cytoplasm upon activation of the p21 promoter, which in turn translocates into the nucleus upon administration of 4-hydroxytamoxifen (OHT). The Cre-activable floxed Rosa26 reporter mouse crossed with the p21-CreERT2 mouse expresses the reporter gene (e.g., LacZ or tdTomato) in CreERT2-expressing cells and their descendants upon p21 promoter activation and OHT administration, thereby allowing lineage tracking of the p21 promoter-activated cells and clarification of tissue turnover after irradiation. In the p21-Cre-ERT2-Rosa26 reporter mouse further crossed with the cancer-prone mouse (e.g., ApcMin/+), it can be revealed whether the resulting tumors are derived from the p21 promoter-activated cells and their descendants upon irradiation and OHT administration. This poster shall describe the current progress in this project.
Primary author
Dr
Nobuyuki Hamada
(Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Tokyo 201-8511, Japan)
Co-authors
Dr
Kensuke Otsuka
(Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Tokyo 201-8511, Japan)
Dr
Motohiro Yamauchi
(Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Tokyo 201-8511, Japan)
Dr
Toshiyasu Iwasaki
(Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Tokyo 201-8511, Japan)
Ms
Yuki Fujimichi
(Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Tokyo 201-8511, Japan)
Ms
Yuko Hoshi
(Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), Tokyo 201-8511, Japan)
