Bystander Response Following High-Dose X-irradiation; Time-dependent Nature of GammaH۲AX Foci and Cell Death Consequences
- سال انتشار: 1402
- محل انتشار: مجله فیزیک و مهندسی پزشکی، دوره: 13، شماره: 1
- کد COI اختصاصی: JR_JBPE-13-1_003
- زبان مقاله: انگلیسی
- تعداد مشاهده: 62
نویسندگان
Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran
Department of Bioscience and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran
Department of Medical Genetics, Medical Biotechnology Institute, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
Radiation Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
چکیده
Background: The paradigm shifts in target theory could be defined as the radiation-triggered bystander response in which the radiation deleterious effects occurred in the adjacent cells. Objective: This study aims to assess bystander response in terms of DNA damage and their possible cell death consequences following high-dose radiotherapy. Temporal characteristics of gH۲AX foci as a manifestation of DNA damage were also evaluated.Material and Methods: In this experimental study, bystander response was investigated in human carcinoma cells of HeLa and HN۵, neighboring those that received high doses. Medium transfer was performed from ۱۰ Gy-irradiated donors to ۱.۵ Gy-irradiated recipients. GammaH۲AX foci, clonogenic and apoptosis assays were investigated. The gH۲AX foci time-point study was implemented ۱, ۴, and ۲۴ h after the medium exchange. Results: DNA damage was enhanced in HeLa and HN۵ bystander cells with the ratio of ۱.۲۷ and ۱.۷۲, respectively, which terminated in more than two-fold clonogenic survival decrease, along with gradual apoptosis increase. GammH۲AX foci temporal characterization revealed maximum foci scoring at the ۱ h time-point in HeLa, and also ۴ h in HN۵, which remained even ۲۴ h after the medium sharing in higher level than the control group. Conclusion: The time-dependent nature of bystander-induced gH۲AX foci as a DNA damage surrogate marker was highlighted with the persistent foci at ۲۴ h. considering an outcome of bystander-induced DNA damage, predominant role of clonogenic cell death was also elicited compared to apoptosis. Moreover, the role of high-dose bystander response observed in the current work clarified bystander potential implications in radiotherapy.کلیدواژه ها
Bystander, High-Dose, GammaH۲AX, DNA Damage, Survival, apoptosisاطلاعات بیشتر در مورد COI
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