bystander response following high-dose x-irradiation; time-dependent nature of gammah2ax foci and cell death consequences

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.