Kinetics of repair in the spinal cord of the rat

• Published in: Radiotherapy and oncology 1997-10, Vol.45 (1), p.55-62
• Main Authors: Landuyt, Willy, Fowler, Jack, Ruifrok, Arnout, Stüben, Georg, van der Kogel, Albert, van der Schueren, Emmanuel
• Format: Article
• Language: English
• Subjects: Animals; Brachytherapy - methods; Confidence Intervals; Dose-Response Relationship, Radiation; Half-time; Kinetics; Male; Radiation damage repair; Radiation Dosage; Radiation Injuries, Experimental; Rats; Spinal cord; Spinal Cord - pathology; Spinal Cord - radiation effects; Spinal Cord Diseases - etiology; Spinal Cord Diseases - prevention & control; Wound Healing
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/S0167-8140(97)00139-4

Purpose: Split dose experiments were carried out with two 2 Gy fractions per day at intervals ranging from 0.5 to 24 h, in order to investigate both the time to complete repair and the detailed kinetics of repair of sublethal damage in the cervical spine of rats. Materials and methods: Male rats of the WAG/Rij strain were irradiated at 2 Gy/min with 18 MV photons to a length of 18 mm of cervical spinal cord. Four hundred twenty-three rats were irradiated without top-up doses to investigate 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 + Δt + 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 days. A mono-exponential component of repair of T 1 2 = 0.25 (95% CI 0.16–0.48) h was determined by direct analysis using all the data and T 1 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 component was demonstrated graphically, with T 1 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. Considering 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) have 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 schedules. Radiother. Oncol. 25: 287–294, 1992) in the spinal cord of Sprague-Dawley rats. Two components have also been reported by others more recently. The present result could, with its graphical interpretation, 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. Fractionation sensitivity of rat cervical spinal cord during radiation retreatment. Radiother. Oncol. 25: 295–300, 1992) in a rela