Bystander Response Following High-Dose X-irradiation; Time-dependent Nature of GammaH2AX Foci and Cell Death Consequences | ||
| Journal of Biomedical Physics and Engineering | ||
| مقاله 3، دوره 13، شماره 1، اردیبهشت 2023، صفحه 17-28 اصل مقاله (3.15 M) | ||
| نوع مقاله: Original Research | ||
| شناسه دیجیتال (DOI): 10.31661/jbpe.v0i0.2001-1053 | ||
| نویسندگان | ||
| Fatemeh Pakniyat1؛ Hossein Mozdarani* 2؛ Hassan Ali Nedaee1، 3؛ Aziz Mahmoudzadeh4؛ Mahdieh Salimi5؛ Somayeh Gholami3 | ||
| 1Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran | ||
| 2Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran | ||
| 3Radiation Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran | ||
| 4Department of Bioscience and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran | ||
| 5Department of Medical Genetics, Medical Biotechnology Institute, National Institute of Genetic Engineering and Biotechnology, 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 gH2AX 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 HN5, neighboring those that received high doses. Medium transfer was performed from 10 Gy-irradiated donors to 1.5 Gy-irradiated recipients. GammaH2AX foci, clonogenic and apoptosis assays were investigated. The gH2AX foci time-point study was implemented 1, 4, and 24 h after the medium exchange. Results: DNA damage was enhanced in HeLa and HN5 bystander cells with the ratio of 1.27 and 1.72, respectively, which terminated in more than two-fold clonogenic survival decrease, along with gradual apoptosis increase. GammH2AX foci temporal characterization revealed maximum foci scoring at the 1 h time-point in HeLa, and also 4 h in HN5, which remained even 24 h after the medium sharing in higher level than the control group. Conclusion: The time-dependent nature of bystander-induced gH2AX foci as a DNA damage surrogate marker was highlighted with the persistent foci at 24 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. | ||
| کلیدواژهها | ||
| Bystander؛ High-Dose؛ GammaH2AX؛ DNA Damage؛ Survival؛ Apoptosis | ||
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