@article{oai:repo.qst.go.jp:00080294,
 author = {Wang, Jun and Kobayashi, Alisa and Ohsawa, Daisuke and Oikawa, Masakazu and Konishi, Teruaki and Kobayashi, Alisa and Ohsawa, Daisuke and Oikawa, Masakazu and Konishi, Teruaki},
 journal = {Radiation Research},
 month = {Jul},
 note = {It has been reported that in low dose irradiated cells, radio-adaptive responses can be induced which make cells refractory to following high dose irradiation. However, whether adaptive responses can be induced in cells whose cytoplasm is hit while nucleus is not targeted remains unknown. In this study, by using the Single Particle Irradiation System to Cells proton microbeam facility at the National Institute of Radiological Sciences (Japan), we found that cytoplasmic irradiation activated the radio-adaptive responses in normal human lung fibroblast WI-38 cells. Our results showed that cytoplasmic irradiation with 500 protons prior to 2 Gy or 6 Gy X-ray broad beam irradiation resulted in obvious decrease of the DNA double-strands breaks levels. Further, the radio-adaptive responses were not induced in cells whose cytoplasm was hit with not higher than 100 protons. And a longer than 6 hours’ time interval between cytoplasmic irradiation and high dose X-ray broad beam irradiation was needed for the induction of adaptive responses. In addition, cytoplasmic irradiation elevated mitochondrial superoxide level, which further enhanced the phosphorylation of ERK 1/2 (Extracellular signal-regulated kinases 1/2) and its mediated nucleus accumulation of NRF2 (nuclear factor (erythroid-derived 2)-like 2). This signaling way contributed to the induction of the radio-adaptive response in cytoplasm irradiated cells as manifested by using the selective scavenger or inhibitors of mitochondrial superoxide, ERK 1/2 and NRF2. Overall, we confirmed that cytoplasmic irradiation was capable to induce radio-adaptive responses, and demonstrated the activated mitochondrial superoxide/ ERK 1/2/ NRF2 signaling was one of the underlying mechanisms. Our results brought interesting information to cytoplasm targeted irradiation induced biological effects.},
 pages = {288--297},
 title = {Cytoplasmic radiation induced radio-adaptive response in human lung fibroblast WI-38 cells},
 volume = {194},
 year = {2020}
}