@article { author = {Pakniyat, Fatemeh and Mozdarani, Hossein and Nedaee, Hassan Ali and Mahmoudzadeh, Aziz and Salimi, Mahdieh and Gholami, Somayeh}, title = {Bystander Response Following High-Dose X-irradiation; Time-dependent Nature of GammaH2AX Foci and Cell Death Consequences}, journal = {Journal of Biomedical Physics and Engineering}, volume = {13}, number = {1}, pages = {17-28}, year = {2023}, publisher = {Shiraz University of Medical Sciences}, issn = {2251-7200}, eissn = {2251-7200}, doi = {10.31661/jbpe.v0i0.2001-1053}, abstract = {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.}, keywords = {Bystander,High-Dose,GammaH2AX,DNA Damage,Survival,apoptosis}, url = {https://jbpe.sums.ac.ir/article_47217.html}, eprint = {https://jbpe.sums.ac.ir/article_47217_af2fecda1b7612c71ed22b45a5f84a22.pdf} }