RADIOSENSITIVITY OF HUMAN CELL-LINES TO SMALL DOSES - ARE THERE SOME CLINICAL IMPLICATIONS

The concept of intrinsic radiosensitivity is now strongly associated w ith the linear-quadratic (LQ) model which is currently the best and th e most reliable method to fit the first three decades of a survival cu rve for both human fibroblast and human tumor cell lines. This approac h has led to the major conclusions that it is the initial part, and no t the distal part, of the survival curve which truly characterizes int rinsic cellular radiosensitivity and there is a correlation between th e parameters describing mainly the initial part of the survival curve (alpha, SF2, ($) over bar D) and the clinical radioresponsiveness. Mor e accurate analysis with flow cytometry or a dynamic microscopic image processing scanner (DMIPS) has allowed further study of the survival curve which has shown two sorts of substructure. On one hand, the over all survival curve of exponentially growing cells is described by two or more sets of alpha, beta parameters (heterogeneity in radiosensitiv ity due to the cell cycle). On the other hand, hypersensitivity at ver y low doses (<0.5 Gy) followed by an increase of the radioresistance o f the whole population at higher doses has also been observed. This ph enomenon is not described by the conventional LQ model and has been in terpreted as an induced radioresistance which seems to be negatively c orrelated with intrinsic radiosensitivity. In clinical radiotherapy, t here are two sorts of response of normal tissues: (1) the early and la te damage and (2) the carcinogenesis. Concerning the first point, the clinically detectable radiation damage appears at doses usually around 20 Gy (in 2-Gy fractions) with the exception of the hemopoietic and t he lymphatic tissues. Therefore, the small doses delivered at the edge s or in the penumbrae of treatment fields in routine radiotherapy cann ot create detectable damage, despite a potentially much higher effect per unit dose, because the total doses are still very small. However, it may be important to bear in mind the possible extra effect of low d oses outside the target volume if regions in the vicinity are subseque ntly retreated. Concerning clinical radiation-induced carcinogenesis, three studies described a higher relative risk associated with small d oses per fraction or very low dose rate. The results and the interpret ation of these studies are discussed.