Impact of dose-rate on the low-dose hyper-radiosensitivity and induced radioresistance (HRS/IRR) response

Abstract

Purpose: To ask whether dose-rate influences low-dose hyper- radiosensitivity and induced radioresistance (HRS/IRR) response in rat colon progressive (PRO) and regressive (REG) cells.

Methods: Clonogenic survival was applied to tumorigenic PRO and non-tumorigenic REG cells irradiated with ⁶⁰Co γ-rays at 0.0025–500 mGy.min⁻¹. Both clonogenic survival and non-homologous end-joining (NHEJ) pathway involved in DNA double-strand breaks (DSB) repair assays were applied to PRO cells irradiated at 25 mGy.min⁻¹ with 75 kV X-rays only.

Results: Irrespective of dose-rates, marked HRS/IRR responses were observed in PRO but not in REG cells. For PRO cells, the doses at which HRS and IRR responses are maximal were dependent on dose-rate; conversely exposure times during which HRS and IRR responses are maximal (t_HRSmax and t_IRRmax) were independent of dose-rate. The t_HRSmax and t_IRRmax values were 23 ± 5 s and 66 ± 7 s (mean ± standard error of the mean [SEM], n = 7), in agreement with literature data. Repair data show that t_HRSmax may correspond to exposure time during which NHEJ is deficient while t_IRRmax may correspond to exposure time during which NHEJ is complete.

Conclusion: HRS response may be maximal if exposure times are shorter than t_HRSmax irrespective of dose, dose-rate and cellular model. Potential application of HRS response in radiotherapy is discussed.

Keywords::

• Hyper-radiosensitivity (HRS) response
• induced radioresistance (IRR) response
• dose-rate
• DSB repair
• tumor cells
• radiotherapy