Hyperfast, early cell response to ionizing radiation

Purpose : To determine whether the oscillatory changes of radiosensitivity which occur within fractions of a second to a few minutes following flash irradiation correlate with an altered incidence of apoptosis, DNA strand breaks or lipid-coupled signalling. Materials and methods : Human tumor cells (SQ-20B, LoVo) or Chinese hamster V79 fibroblasts were exposed to split-dose, pulse irradiation with 3.5 MeV electrons at high dose-rate (12 or 120Gys -1) and the effects assessed by clonogenic assays, analysis of DNA cleavage and microscopic observation. Results : The processes underlying oscillatory radiation response were saturable, but did not correlate with an increased incidence of DNA single- or double-strand breaks or apoptosis. N -acetylcysteine and inhibitors of lipid-derived signalling also failed to alter oscillatory response. However, this response did correlate with phenotypic alterations evoking mitotic or delayed cell death. Furthermore, high dose-rate irradiation provided a lower level of instability than protracted γ-ray irradiation. Conclusions : It is proposed that the early steps of DNA damage recognition and repair following priming radiation exposure bring about rapid, synchronous remodeling of chromatin, evoking enhanced chromosome damage upon re-irradiation.