Radiation-induced bystander effect (RIBE) has been identified as an important contributing factor to tumor resistance and normal tissue damage. However, the RIBE in cancer and normal cells under hypoxia remain unclear. In this study, confluent A549 cancer and WI-38 normal cells were subjected to condition of hypoxia or normoxia, before exposure to high-LET protons microbeam. After 6 h incubation, cells were harvested and assayed for colony formation, micronucleus formation, chromosome aberration and western blotting. Our results show that there were differences of RIBE in bystander A549 and WI-38 cells under hypoxia and normoxia. The differences were also observed in the roles of HIF-1α expression in bystander A549 and WI-38 cells under both conditions. Furthermore, inhibition of gap junction intercellular communication (GJIC) showed a decrease in toxicity of hypoxia-treated bystander A549 cells, but increased in bystander WI-38 cells. These findings clearly support that GJIC protection of bystander normal cells from toxicity while enhancing in bystander cancer cells. Together, the data show a promising strategy for high-LET radiation in designing an entire new line of drugs, either increase or restore GJIC in bystander cancer cells which in turn leads to enhancement of radiation accuracy for treatment of hypoxic tumors.
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February 2022
REGULAR ARTICLES|
October 11 2021
Hypoxia and Proton microbeam: Role of Gap Junction Intercellular Communication in Inducing Bystander Responses on Human Lung Cancer Cells and Normal Cells
Narongchai Autsavapromporn;
Narongchai Autsavapromporn
1
a Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200 Thailand
1 Address for correspondence: Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; email: [email protected].
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Alisa Kobayashi;
Alisa Kobayashi
b Single Cell Radiation Biology Group, Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Inage-ku, Chiba 263-8555, Japan
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Cuihua Liu;
Cuihua Liu
b Single Cell Radiation Biology Group, Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Inage-ku, Chiba 263-8555, Japan
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Churdsak Jaikang;
Churdsak Jaikang
c Toxicology Section, Department of Forensic Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
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Tengku Ahbrizal Tengku Ahmad;
Tengku Ahbrizal Tengku Ahmad
d Radiation Safety and Health Division, Malaysian Nuclear Agency, Bangi, 43000 Kajang, Selangor, Malaysia
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Masakazu Oikawa;
Masakazu Oikawa
b Single Cell Radiation Biology Group, Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Inage-ku, Chiba 263-8555, Japan
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Teruaki Konishi
Teruaki Konishi
b Single Cell Radiation Biology Group, Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Inage-ku, Chiba 263-8555, Japan
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Radiat Res (2022) 197 (2): 122–130.
Article history
Received:
May 26 2021
Accepted:
September 23 2021
Citation
Narongchai Autsavapromporn, Alisa Kobayashi, Cuihua Liu, Churdsak Jaikang, Tengku Ahbrizal Tengku Ahmad, Masakazu Oikawa, Teruaki Konishi; Hypoxia and Proton microbeam: Role of Gap Junction Intercellular Communication in Inducing Bystander Responses on Human Lung Cancer Cells and Normal Cells. Radiat Res 1 February 2022; 197 (2): 122–130. doi: https://doi.org/10.1667/RADE-21-00112.1
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