Lack of correlation between basal cell survival and gross response in irradiated swine skin

The relationship between basal cell survival and gross response in irradiated swine skin was tested by comparing dose survival curves derived from time-dose isoeffect data with curves obtained directly from basal cell counts in histological sections. Assuming equal effect per exposure and constant cell survival at isoeffect, best-fitting single-hit multi-target and linear-quadratic response curves were determined for time-dose schedules resulting in non-healing of 50% of irradiated fields. Basal cell survivals for single doses of 970, 1649, 2231, and 2619 rad were estimated 1) by counting regenerating islands and 2) by monitoring total basal cell counts through time. The dose survival curve derived from the isoeffect data was steeper than the curve obtained from direct basal cell counts. Furthermore, the direct basal cell survival curve extrapolates to less than 100% at zero dose, indicating the presence of a resistant basal cell subpopulation. The data show that the isoeffect in this case is not strongly coupled to basal cell survival. Rather, the probability of healing of an irradiated field is more sensitive to the dose per fraction than is basal cell survival, implying a contribution to non-healing from damage to stromal elements such as the capillary endothelium.