The combined effects of sublethal damage repair, cellular repopulation and redistribution in the mitotic cycle. II. The dependency of radiosensitivity parameters alpha, beta and t(0) on biological age for Chinese hamster V79 cells.

In this paper, an analytical formalism, designated the R3 model, is applied to the problem of understanding changes in cellular radiosensitivity as a function of the position of the cell in the generation cycle. The model describes the survival probability for cells exposed to ionizing radiation and incorporates the effects of sublethal damage repair, repopulation and redistribution in the cell cycle. The importance of this problem stems in part from the increasing reliance on in vitro, single-cell model systems to design optimal radiotherapy treatment protocols, and in particular from the fact that arguments used to justify newer methodologies often bear quite heavily on descriptors (e.g. alpha and beta) meant to be employed for cells homogeneous in radiosensitivity--a situation hardly applicable to tissues. From the analysis of two sets of data for Chinese hamster V79 cells (Sinclair and Morton, Nature 205, 247-250, 1964; Gillespie et al., Radiat. Res. 64, 353-364, 1975) the linear-quadratic parameters (alpha, beta) are obtained as a function of cell cycle age. The results indicate substantial variation of these parameters inside each phase of the cycle. Moreover, it is noticeable that alpha and beta show different patterns of variation during the cycle and therefore the ratio alpha/beta will also change. At the regions of the cycle where beta is large (the beginning of G1 phase, at the G1/S-phase border and during G2 phase) dose-rate effects would be expected to be important. The data for V79 cells are consistent with the view that sublethal damage repair occurs predominantly in S phase, with very little (if any) repair in the other phases of the cycle.