EFFECT OF SMALL DOSES PER FRACTION IN RAT SPINAL-CORD - INFLUENCE OF INITIAL VS FINAL TOP-UP DOSES

Previous data suggested that the linear-quadratic (LQ) model underesti mated the sparing effect of small doses per fraction on the radiation tolerance of rat cervical spinal cord when 24 h was allowed between fr actions for repair. In these experiments, animals had been given initi al top-up doses consisting of 3 daily fractions of 9 Gy to represent 7 5% tolerance, followed by small fractionated doses in 1, 10, 20, 30 an d 40 fractions given once daily. The end-point was forelimb paralysis secondary to white matter necrosis. To assess the possible perturbatio n of the initial top-up doses on the biological system, an experiment was performed with the small fractionated doses given initially, follo wed by the same top-up (final top-up) doses. The ED50s for 1, 10, 20, 30 and 40 fractions followed by final top-up doses were 9.5 +/- 0.3, 2 2.6 +/- 0.6, 32.4 +/- 0.6, 37.7 +/- 0.8 and 41.7 +/- 0.9 Gy, respectiv ely; the corresponding ED50s obtained from the initial top-up experime nt were 10.0 +/- 0.4, 20.7 +/- 0.5, 30.0 +/- 0.8, 37.0 +/- 0.8 and 39. 9 +/- 0.7 Gy for 1, 10, 20, 30 and 40 fractions, respectively. Using t he direct method of analysis and assuming complete repair between frac tions, data from both experiments were not adequately described by the LQ model, which gave small alpha/beta values of 0.97 Gy for the initi al top-up experiment and 1.23 Gy for the final top-up experiment, in c ontrast to an alpha/beta value of 2.41 Gy for the experiment with full course fractionation, fraction sizes down to 2 Gy. Direct analysis of the data from both top-up experiments and the experiment with full co urse fractionation to the NSD formula gave an identical exponent of 0. 41 for the fraction number. It is concluded that the sequence of top-u p doses does not influence experimental outcome and that regardless of the sequence of top-up doses, the LQ model is inadequate and underest imates the sparing effect of small doses per fraction in the rat spina l cord when a 24-h interval is allowed between each fraction for repai r of sublethal damage.