Abstract
We demonstrated that low dose pulsed radiation (0.25 Gy) at a high-dose-rate, even for very short intervals (10 s), decreases cell survival to a greater extent than single exposure to a similar total dose and dose rate. The objective of this study was to clarify whether high-dose-rate pulsed radiation is effective against SAS-R, a clinically relevant radioresistant cell line. Cell survival following high-dose-rate pulsed radiation was evaluated via a colony assay. Flow cytometry was utilized to evaluate γH2AX, a molecular marker of DNA double-strand breaks and delayed reactive oxygen species (ROS) associated with radiation-induced apoptosis. Increased cytotoxicity was observed in SAS-R and parent SAS cells in response to high dose rate pulsed radiation compared to single dose, as determined by colony assays. Residual γH2AX in both cells subjected to high-dose-rate pulsed radiation showed a tendency to increase, with a significant increase observed in SAS cells at 72 h. In addition, high-dose-rate pulsed radiation increased delayed ROS more than the single exposure did. These results indicate that high-dose-rate pulsed radiation was associated with residual γH2AX and delayed ROS, and high-dose-rate pulsed radiation may be used as an effective radiotherapy procedure against radioresistant cells.
Highlights
Elimination of radioresistant cancer cells poses a serious issue in radiotherapy, because radioresistant cells, as well as hypoxic cells that are resistant to radiation, survive after radiation therapy, leading to cancer recurrence or metastasis [1,2]
In a previous study [17], high-dose-rate PR amounting to a total dose of 8 Gy reduced cell survival by less than approximately 40% compared with a single exposure, but no significant changes were observed in apoptosis or cell cycle analysis
Relevant radioresistant SAS-R [18,19] cells were established from the parental cell line SAS
Summary
Elimination of radioresistant cancer cells poses a serious issue in radiotherapy, because radioresistant cells, as well as hypoxic cells that are resistant to radiation, survive after radiation therapy, leading to cancer recurrence or metastasis [1,2]. A method that is effective against radioresistant cells without involving drugs may improve the success rate of radiation therapy and ensure its success. The low-dose region contains a radiosensitive region termed the hyper-radiosensitivity (HRS) region, and the application of low doses in radiotherapy to improve the radiosensitivity of cancer cells has been studied. PLDR [11] was developed as an irradiation method that involves applying HRS and reverses dose rate effects. Due to difficulties in assessing the effects of low doses, the mechanism underlying HRS remains unclear. The effects of multiple low dose irradiations on radioresistant cancer cells as well as the mechanisms underlying these effects remain unclarified
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
