RRC ID 62963
Author Wang J, Kobayashi A, Ohsawa D, Oikawa M, Konishi T.
Title Cytoplasmic Radiation Induced Radio-Adaptive Response in Human Lung Fibroblast WI-38 Cells.
Journal Radiat Res
Abstract It has been reported that in cells exposed to low-dose radiation, radio-adaptive responses can be induced which make irradiated cells refractory to subsequent high-dose irradiation. However, whether adaptive responses are possible when only the cytoplasm, not the nucleus, of the cell is exposed to radiation is still unclear. In this study, using the proton microbeam facility at the National Institute of Radiological Sciences (Japan), we found that cytoplasmic irradiation activates radio-adaptive responses in normal human lung fibroblast WI-38 cells. Our results showed that when cells received cytoplasmic irradiation with 500 protons prior to 2 Gy or 6 Gy X-ray broad-beam irradiation, the DNA double-strand break levels were significantly reduced. In contrast, at cytoplasmic irradiation with less than 100 protons, the radio-adaptive response was not detected. Moreover, the time interval between cytoplasmic irradiation and whole-cell X-ray irradiation should be longer than 6 h for the induction of adaptive responses. In addition, cytoplasmic irradiation elevated the level of cellular mitochondrial superoxide, which enhanced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK 1/2) and its mediated nuclear accumulation of nuclear factor (erythroid-derived 2)-like 2 (NRF2). This signaling pathway contributed to cytoplasmic irradiation-induced adaptive response as supported by the observations that treatment with the mitochondrial superoxide scavenger mito-tempol, ERK 1/2 inhibitor U0126 or NRF2 inhibitor ML385 could repress the adaptive response. Overall, we showed that cytoplasmic irradiation induces radio-adaptive responses and that mitochondrial superoxide/ERK 1/2/NRF2 signaling is a mechanism. Our results provide new information on the biological effects induced by cytoplasm-targeted irradiation.
Volume 194(3)
Pages 288-297
Published 2020-9-16
DOI 10.1667/RR15575.1
PII 441606
PMID 32942306
MeSH Cell Line Cytoplasm / metabolism* Cytoplasm / radiation effects* DNA Breaks, Double-Stranded / radiation effects Dose-Response Relationship, Radiation Fibroblasts / cytology* Fibroblasts / radiation effects* Humans Mitochondria / metabolism Mitochondria / radiation effects Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism NF-E2-Related Factor 2 / metabolism Superoxides / metabolism
IF 2.657
Human and Animal Cells WI-38(RCB0702)