Studies of dose-fractionation on early and late responses in pig skin: a reappraisal of the importance of the overall treatment time and its effects on radiosensitization and incomplete repair.

Studies in pig skin have examined the effects of dose fractionation on the acute radiation response. The variation in ED50 values for moist desquamation for doses given as 1-48 fractions over less than or equal to 16 days were best fitted by a log-log plot of iso-effect dose against the number of fractions; the slope of this plot indicated a fraction number exponent (N) of 0.42 +/- 0.007. Based on the assumptions made in applying the linear-quadratic (LQ) model, the alpha/beta ratio was found to decrease with decreasing per fraction: for doses given as 6-27 Gy per fractions the alpha/beta ratio was 8.74 +/- 0.48 Gy, whereas for doses of 2.55-6 Gy per fraction it was only 0.85 +/- 0.29 Gy. A simple approach to a time factor could not be used to calculate iso-effect doses for acute reactions in pig skin when treatment time was increased from less than or equal to 16 days to 28-39 days. This was due to the opposing effects of radiosensitization and repopulation when the cell cycle time of epidermal basal cells was shortened. For late dermal necrosis in pig skin, repair of sublethal damage was not completed in 24 hr. This finding has a significant effect on the interpretation of the results of fractionation studies using this late endpoint. Expressed in terms of a simple power-law function, there was a significant change in the fraction number exponent "N" from 0.43 +/- 0.007 to 0.37 +/- 0.006 for the complete and incomplete repair data, respectively. Many of the fractionation effects reported for acute and late damage to pig skin would appear to be in excellent agreement with those for human skin.