Establishment of acquired radioresistant cells to fractionated radiation from hTERT-immortalized normal human epithelial cell

Senescence-like growth arrest (SLGA), which is a radiation-induced cell death pathway, is induced in immortalized normal human epithelial cell (hTERT-RPE1) by the daily fractionated X-irradiation with 1.5 Gy within 30 times. We here demonstrate that pre-treatment induces acquired radioresistance (ARR) that can survive from the lethal fractionated radiation. The parent cells were daily fractionated with 1.5 Gy for 5 d and then incubated for 7 d without fractionated radiation. After this, the daily fractionated radiation with 1.5 Gy was restarted. A small population of surviving cells appeared after 30 times of the daily fractionated radiation was completed and they were continuously growing up to 120 times of the daily fractionated radiation (RPE1–1.5Fr). We confirmed a higher basal expression level of p53, which functions in the activation of the SLGA pathway but fails to further accumulate after 1.5 Gy of single irradiation in RPE1–1.5Fr. It is the first report to induce ARR phenotype for fractionated radiation in normal human cells.