@misc{oai:repo.qst.go.jp:00076614,
 author = {Autsavapromporn, Narongchai and Liu, Cuihua and Kobayashi, Alisa and Ahbrizal Farizal Tengku  Ahmad, Tengku and Konishi, Teruaki and Liu, Cuihua and Kobayashi, Alisa and Konishi, Teruaki},
 month = {Aug},
 note = {Background: Hypoxia and proton-induced bystander response is an important contributory factor to tumor resistance and normal tissue damage, subsequently lead to treatment failure and affect the quality of life. Previously, we have shown that gap-junction intercellular communication (GJIC) mediates the propagation of protective or stress responses from irradiated to bystander cells.
Aim: The aim of this study is to investigate the role of GJIC and hypoxia-induced bystander response  in lung cancer and normal human lung cells under normoxic and hypoxic conditions exposed to proton microbeams.
Methods: Human non-small cell lung adenocarcinoma cells (A549) and normal lung fibroblasts (WI-38)    were incubated either in normoxic or hypoxic conditions for 2 days. Prior to proton microbeam irradiation (LET 11 keV/m), the culture media was removed  and irradiation is carried out at mean absorbed doses of 2 Gy by which 0.04-0.15% of the cells were directly targeted by protons. Following 6 hour incubation under  normoxic and hypoxic conditions, the cells were harvested and assayed for micronucleus formation and chromosomal aberration.
Results: The results showed that the levels of DNA damage and chromosomal aberrations in bystander hypoxia A549 cells decreased compared with cells under normoxia. On the other hand, the comparison between A549 cancer and WI-38 normal cells under hypoxia showed increased of DNA damage and dicentric chromosomes in A549 cells, but not in WI-38 cells. Interestingly, downregulation of GJIC decreased toxicity in A549 cells but increased it in WI-38 cells. This result indicates that GJIC plays a role in transmitting of protective or stress signaling between irradiated to bystander cells. Therefore, GJIC protects WI-38 cells from toxicity while enhancing it in A549 cells.
Conclusion: These results show for the first time that the hypoxia-induced bystander responses is differs between cancer and normal cells, and GJIC play a role in influencing the radiosensitivity of hypoxic cancer cells against radiation., 16th International Congress of Radiation Research},
 title = {Hypoxia and proton microbeams: Role of gap junction communication in inducing bystander response on human lung cancer and normal human lung cells},
 year = {2019}
}