Relationship of clonogenic cells and “tumour-rescuing cells”, modelled in irradiated spheroidsin vitro

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Abstract
There is interest in the extent to which one can relate the gross response of a tumour to the behaviour of clonogenic cells within that tumour. Attempts have been made to derive values for the number and sensitivity of “tumour-rescuing cells” (TRC), from the shapes of dose-incidence curves for local control of tumours in animals (e.g. Wheldon et al, 1977) and man (Andrews & Mossman, 1976; Moore et al, 1983). Plainly, knowledge of the behaviour of the last few cells that actually determine whether a tumour regrows or not, and which are often experimentally inaccessible, is important. Characteristically, the D0s of cell survival curves derived from assays of gross response to single doses of radiation are higher, by factors of up to 2 or 3, than those for clonogenic cells measured by excision/dissociation assays following relatively high doses of radiation (Moore et al, 1983). In consequence the derived numbers of TRC are lower, by orders of magnitude, than the numbers of clonogenic cells. Such discrepancies may reflect a true distinction between the radiobiology of clonogenic cells and TRC, but at present it is usually assumed that the differences result from heterogeneity in cell numbers and sensitivity between tumours in an experimental group, inadequate numbers of animals (or patients) per group, or variations in radiation dose received (as analysed by Porter, 1980), all tending to lead to a flattening of “cure” curves.