Mechanisms of cell reproductive death and shapes of radiation dose--survival curves of mammalian cells

Abstract

A 'paired dsb' mechanism of action for cell reproductive death by ionizing radiations is proposed, which allows interpretation of differences in shapes of survival curves caused by variation of linear energy transfer of the radiation, by the stage in the cell cycle, but cell culture conditions and by sensitizing and protecting compounds. It is based on the analysis of shapes of survival curves in terms of S(D)/S(O) = exp - (a1D + a2D2) and the suggestion that paired dsb in DNA, produced within distances of the order of 10 nm, are efficient in initiating the sequence of events causing cell reproductive death by individual particle tracks. Part of the lethality may result from two dsb's produced by single tracks at larger distances, and this might constitute potentially lethal damage which in favourable conditions can be repaired. Thus, the initial slope of a survival curve is not independent of the repair capacity of a cell, but indeed can be modified by cell conditions. The damage causing the quadratic term in the survival equation may be interpreted as a consequence of two dsb produced by two different ionizing particles, although other interactions cannot be excluded. The suggested mechanism of 'paired dsb' damage is consistent with information concerning the LET dependence of different effects in cells and their constituents.