DNA damage and the bystander response in tumor and normal cells exposed to X-rays

- High and low dose and dose rates of X-rays induced DNA damage and cyclins were analyzed.
- High dose and dose rate irradiated cells, their bystanders exhibit high levels of γ-H2AX and p53ser15.
- Induced γ-H2AX, p53ser15 and cyclins do not significantly differ at low dose and low dose rate exposures.
- P53ser15 showed differential expression at 24 h of post-exposure to low dose and dose rate X-rays.
- γ-H2AX, p53ser15 and cyclins expression is dependent on the ATM status of the cell lines.

Monolayer and suspension cultures of tumor (BMG-1, CCRF-CEM), normal (AG1522, HADF, lymphocytes) and ATM-mutant (GM4405) human cells were exposed to X-rays at doses used in radiotherapy (high dose and high dose-rate) or radiological imaging (low dose and low dose-rate). Radiation-induced DNA damage, its persistence, and possible bystander effects were evaluated, based on DNA damage markers (γ-H2AX, p53ser15) and cell-cycle-specific cyclins (cyclin B1 and cyclin D1). Dose-dependent DNA damage and a dose-independent bystander response were seen after exposure to high dose and high dose-rate radiation. The level of induced damage (expression of p53ser15, γ-H2AX) depended on ATM status. However, low dose and dose-rate exposures neither increased expression of marker proteins nor induced a bystander response, except in the CCRF-CEM cells. Bystander effects after high-dose irradiation may contribute to stochastic and deterministic effects. Precautions to protect unexposed regions or to inhibit transmission of DNA damage signaling might reduce radiation risks.