@article{oai:repo.qst.go.jp:00049342,
 author = {Autsavapromporn, Narongchai and Liu, Cuihua and Kobayashi, Alisa and Ahbrizal Farizal Tengku Ahmad, Tengku and Oikawa, Masakazu and Dukaew, Nahathai and Wang, Jun and Wongnoppavich, Ariyaphong and Konishi, Teruaki and Liu, Cuihua and Kobayashi, Alisa and Oikawa, Masakazu and Konishi, Teruaki},
 issue = {2},
 journal = {Radiation Research},
 month = {Dec},
 note = {Increased understanding of radiation-induced secondary bystander effect (RISBE) is crucial for particle radiation therapy (RT) since it likely contributes to normal tissue injury and tumor recurrence leading to the treatment failure. In this work, we have developed a simple method based on proton microbeam and a transwell insert co-culture system to elucidate the RISBE between irradiated human lung cancer cells and non-irradiated human normal cells. In our experiment, A549 lung cancer cells received a single-dose or fractionated doses of proton microbeam to generate the primary bystander cells. These cells were then seeded on the top of the insert with secondary bystander WI-38 normal cells growing underneath in the presence or absence of gap junction intercellular communication (GJIC) inhibitor, AGA. Cells were co-cultured then harvested and assayed for micronuclei formation. A fractionated doses of protons caused less DNA damage in the secondary bystander WI-38 cells than a single-dose radiation. These results indicated that the rescue effect might be involved in the repair of DNA damages in the secondary bystander WI-38 cells. Interestingly, the damaging effect in the secondary bystander normal cells could be eliminated by the treatment with AGA. Overall, this work is the first  attempt to demonstrate that GJIC plays a major role in the RISBE generated from the primary bystander cancer cells, which is directly relevant in the 5R’s of fractionation RT.},
 pages = {211--216},
 title = {Emerging Role of Secondary Bystander Effects Induced by  Fractionated Protons Microbeam Irradiation},
 volume = {191},
 year = {2018}
}