A critical appraisal of clonogenic survival assays in the evaluation of radiation damage to normal tissues.

Assessment of radiation damage to normal tissues in terms of dose-response curves for infinite proliferative potential ("survival curves") does not take into account the decrease with increasing dose of the multiplication rate of the clonogenic and non-clonogenic (radiation-sterilized) cells which may be implicated in the expression of the damage to tissue function or gross appearance. While radiation selectively lowers the chance of successful mitotic divisions, other anticancer agents may in addition interfere with different cellular processes. Comparisons of effectiveness of radiation with that of other modalities should not therefore be limited to analysis of survival curves. Assays of cell "survival" in self-renewing normal tissues in situ often define properties of a non-random sample of the clonogens. The nature of repair associated with the post-irradiation delay in performance of transplantation assays for normal clonogenic cells remains unclear. Dose-response relationships for functional impairment or gross damage to tissue, especially those obtained by irradiation with many fractions, do not necessarily yield to interpretation in terms of clonogenic cell "survival".