Survival curves for normal-tissue clonogens: a comparison of assessments using in vitro, transplantation, or in situ techniques

A survey of survival curves in the literature, for clonogenic cells (clonogens) in normal tissues, highlights the following features: the sensitivity of some human and dog clonogens apparently is greater than that of their counterparts in mice and sheep, assessed in vitro. However, this should be interpreted with caution because of the possibility of cell selection and the ability to modify sensitivity markedly in some systems by variations in growth conditions; extrapolation numbers are in general higher when assessed in vivo than in vitro. This is due partly to the lack of measurements of repair of potentially-lethal damage using many assays in vitro. This feature increases the extrapolation number when measured using transplantation assays in vivo; epithelial clonogens in vivo demonstrate a remarkable similarity in sensitivity between tissues. The range is similar for clonogens assayed in situ or by transplantation, and this argues against the possibility that a resistant subpopulation may be selected in most assays in situ. It is emphasized from the comparisons that caution must be exercised in extrapolating results, obtained for clonogens assayed in vitro or by transplantation in vivo, to the situation in situ.