Estimation of repair parameters in mouse lip mucosa during continuous and fractionated low dose-rate irradiation

Abstract

The present study investigated the effect of fractionated low dose-rate (FLDR) treatments in mouse lip mucosa, a typically early reacting tissue. The relation between dose-rate and fractionation effect has been assessed with various interfraction intervals and dose-rates. A fixed overall treatment time of 10 h has been used for the present continuous and fractionated irradiation experiments with corresponding dose-rates of 3.1-84 Gy/h. Sophisticated mathematical models are now available to estimate repair parameters from data derived with different fraction numbers, fraction sizes and dose-rates. These formulas, allowing the calculations of isoeffect relationships are based on the incomplete repair model and assume that repair can operationally be described by a monoexponential function. A further assumption of these models is that repair of sublethal damage follows the same kinetics during irradiation and between fractions. The present FLDR experiments with small interfraction spacing were performed to investigate the validity of these assumptions and consequently the applicability of the models. In addition, it has been assessed whether the experimental approach of investigating repair kinetics as such [high dose-rate (HDR) split-course vs. continuous low dose-rate (CLDR) or FLDR] influences the estimation of these parameters, as has been suggested from the analysis of in vitro studies. Using the mucosal desquamation endpoint, virtually identical repair parameters have however been estimated with different approaches (alpha/beta = 14.1-18.2 Gy, T1/2 = 28-37 min). The available isoeffect models seem to be applicable to the present experimental data and might after further experimental tests also involving late reacting tissues, be a useful tool for clinical isoeffect calculations.