@article{oai:repo.qst.go.jp:00049555,
 author = {Konishi, Teruaki and Kobayashi, Alisa and Ahbrizal Farizal Tengku Ahmad, Tengku and Wang, Jun and Konishi, Teruaki and Kobayashi, Alisa},
 issue = {4},
 journal = {Journal of Radiation and Cancer Research},
 month = {Dec},
 note = {Direct exposure of the nucleus to radiation, is the primary cause of various radio-biological effects. However, the cytoplasm is equally exposed to radiation  during treatments that result in activation of intra-cellular response. Thus, the present study is aimed at investigating 1) whether cytoplasmic irradiation affect DSB repair, when the cytoplasm (C) and nucleus (N) is irradiated sequentially, and 2) whether the cytoplasmic irradiation alone is sufficient to induce DNA double strand breaks (DSB) in the nucleus. Material and Methods: To distinguish the radiobiological effects between nuclear and cytoplasmic irradiation, all the experiments were conducted using the SPICE-NIRS microbeam (SPICE), that can target precisely the N and/or C with desired number of 3.4 MeV protons. We examined the kinetics of DSB repair in WI-38 normal human fibroblast cells that were irradiated by microbeam targeted to the N, C, or N+C. Cells were fixed at various time points between 1 to 24 hours post-irradiation. Subsequently, they were immunostained with antibodies against γ-H2AX, a DSB marker, and imaged, to quantify the residual DSB in each nucleus. Results: Microbeam irradiation induced significant γ-H2AX, directly proportional to the number of protons delivered per N. In the C-targeted cells, γ-H2AX levels did not increase significantly, compared to controls, 1-hour post irradiation. However, 4 hours post-irradiation, γ-H2AX levels were significantly increased in C-targeted cells, compared to non-irradiated controls, and the increase was proportional to the number of protons delivered. Cells irradiated with 500 protons per N, showed lowered residual γ-H2AX levels in N+C cells additionally irradiated with 500 or 1000 protons targeted to the C, 16 hours and 24 hours post-irradiation, respectively. Conclusion: Our results suggest that cytoplasmic damage triggers enhanced repair of DSBs that are induced upon nuclear irradiation},
 pages = {183--189},
 title = {Enhanced DNA Double Strand Break Repair Triggered by Microbeam Irradiation Induced Cytoplasmic Damage},
 volume = {9},
 year = {2018}
}