Hyperfast, early cell response to ionizing radiation

Purpose: To determine whether the oscillatory changes of radiosensitivity w hich occur within fractions of a second to a few minutes following flash ir radiation correlate with an altered incidence of apoptosis, DNA strand brea ks 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 120 Gy s(-1)) and the effects assessed b y clonogenic assays, analysis of DNA cleavage and microscopic observation. Results: The processes underlying oscillatory radiation response were satur able, but did not correlate with an increased incidence of DNA single- or d ouble-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 dela yed cell death. Furthermore, high dose-rate irradiation provided a lower le vel of instability than protracted gamma-ray irradiation. Conclusions: It is proposed that the early steps of DNA damage recognition and repair following priming radiation exposure bring about rapid, synchron ous remodeling of chromatin, evoking enhanced chromosome damage upon re-irr adiation.