Can cell survival parameters be deduced from non clonogenic assays of radiation damage to normal tissues?

Abstract

Though dose-response curves for large scale radiation injury to tissues are undoubtedly related to survival curves for clonogenic cells, the relationship between the two sets of curves is not necessarily simple. Sterilization of clonogenic cells occurs near-instantaneously by comparison with the protracted lag period for gross injury to tissues. Moreover, with some types of macroscopic damage, the shapes of the dose-response curves may depend on time of assay. Changes in the area or volume of irradiated tissue may also influence the shapes of these curves. The temporal pattern of expression of large scale injury also varies between tissues, and two distinct groups can be recognized. In rapidly proliferating tissues, the lag period is almost independent of dose, whilst in slowly proliferating tissues, it is inversely proportional to dose. This might be explained by invoking differences in corresponding proliferative structures of the tissues (Three compartmental Type H versus One compartmental Type F proliferative organization). For the second group of tissues, in particular, mathematical modelling suggests a systematic dissociation of the dose-response curves for clonogenic cell survival and for large scale injury. This dissociation, which arises even in the case of single doses, may be even more important when radiation is fractionated. In particular, it may be difficult to disentangle the contributions made to inter-fraction sparing by cellular repair processes and by proliferation-related factors.