KINETICS OF REPAIR IN THE SPINAL-CORD OF THE RAT

Purpose: Split dose experiments were carried out with two 2 Gy fractio ns per day at intervals ranging from 0.5 to 24 h, in order to investig ate both the time to complete repair and the detailed kinetics of repa ir of sublethal damage in the cervical spine of rats. Materials and me thods: Male rats of the WAG/Rij strain were irradiated at 2 Gy/min wit h 18 MV photons to a length of 18 mm of cervical spinal cord. Four hun dred twenty-three rats were irradiated without top-up doses to investi gate whether repair was complete by 24 h or whether any slow repair or proliferation occurred up to 50 days after irradiation. Three hundred seventy-nine rats were also irradiated in split dose (2 Gy + Delta t + 2 Gy each day) experiments, with intervals of 0.5, 1, 2, 4, 8 and 24 h. The split dose irradiations were followed by a single top-up dose of 15 Gy (producing about half the total damage). Results: Repair was complete by 24 h as the ED50 values were the same at 1, 11 and 50 day intervals for two large fractions, and for 10 fractions in 10 or 50 da ys. A mono-exponential component of repair of T1/2 = 0.25 (95% CI 0.16 -0.48) h was determined by direct analysis using all the data and T1/2 = 0.37 (0.28-0.53) h for the split 2 Gy doses with top-up only. A bi- exponential analysis did not fit better. The presence of a second comp onent was demonstrated graphically, with T1/2 of about 6.5 h but with a wide confidence interval from near 0 to 13 h. However, the 24 h ED50 was significantly different from all ED50s except the 8 h value. Cons idering all data together, an upper limit of about 7 h could be placed on any long component, or else repair could not be complete by 24 h. Discussion and conclusions: Two components of repair (0.7 and 3.8 h) h ave been reported by Ang et al. (Ang, K.K., Jiang, G.L., Guttenberger, R., Thames, H.D., Stephens, L.C., Smith, C.D. and Feng, Y. Impact of spinal cord repair kinetics on the practice of altered fractionation s chedules. Radiother. Oncol. 25:287-294, 1992) in the spinal cord of Sp rague-Dawley rats. Two components have also been reported by others mo re recently. The present result could, with its graphical interpretati on, agree in principle, but with a shorter fast component and a longer slow component. A slow component of 5.5 h was reported by Ruifrok et al. (Ruifrok, A.C.C., Kleiboer, B.J. and van der Kogel, A.J. Fractiona tion sensitivity of rat cervical spinal cord during radiation retreatm ent. Radiother. Oncol. 25:295-300, 1992) in a related strain of WAG/Ri j rats. The possible presence of a slower component than Ang et al.'s 3.8 h might help to explain the four myelopathies observed in the pilo t studies for the CHART clinical trial. The presence of the definite f ast component (<0.5 h) could have important consequences when pulsed b rachytherapy is used to replace continuous low dose rate irradiation. (C) 1997 Elsevier Science Ireland Ltd.