Bystander Response Following High-Dose X-irradiation; Time-dependent Nature of GammaH۲AX Foci and Cell Death Consequences

سال انتشار: 1402
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 55

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شناسه ملی سند علمی:

JR_JBPE-13-1_003

تاریخ نمایه سازی: 30 دی 1402

چکیده مقاله:

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.

نویسندگان

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Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran

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Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

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Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran

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Department of Bioscience and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran

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Department of Medical Genetics, Medical Biotechnology Institute, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

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Radiation Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

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