Early cell response to radiation

The early steps of cellular radiation response have been investigated using a linear electron accelerator operated in a split-dose mode, in such a way that the time intervals between pulse exposures to relativistic electrons ranged from fractions of a second to a few minutes. The initial dose brought about large, synchronous changes in radiation sensitivity and generated a tetra-phasic, W-shaped time-dependent profile of cell survival upon the second radiation exposure. While this time-related process was observed in most cell lines investigated, its kinetic parameters varied significantly from one cell line to the other. The number of DNA strand breaks (neutral and alkaline DNA filter elution) and the level of apoptosis (gel electrophoresis and flow cytometry) induced at the different phases of the time-dependent profile showed no relationship with the w-effect. It is presently hypothesized that mechanisms involved in molecular recognition of radio-induced lesions and initiation of genomic instability play a major role in this effect. Whatever the mechanism involved, the split-dose irradiation in the range of seconds enables dissecting the early steps of radiation response. The relevance of the W-effect to radiation therapy and technical drawbacks are discussed. (author)