ht. J. Radiamn Oncology Bid Phys.. Vol. 24. pp. W-5 IO Printed in the U.S.A. All rights reserved. 0364J-3016/92 $5.00 + .oO Copyri@t Q 1992 Pergamon Press Ltd ?? zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Biology Original Contribution zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA RADIATION TOLERANCE AND FRACTIONATION SENSITIVITY OF THE DEVELOPING RAT CERVICAL SPINAL CORD ARNOUT C. C. RUIFROK, PH.D., BERT J. KLEIBOER, B.Sc. AND ALBERT J. VAN DER KOGEL, PH.D. Institute of Radiotherapy, University of Nijmegen, The Netherlands To investigate the influence of age at irradiation on single dose radiation tolerance and fractionation sensitivity, the cervical spinal cord of rats was irradiated at the age of 1 week and at 15-18 weeks (adult). While the main histological lesions seem to be comparable after irradiation at the two ages, differences were found in single dose tolerance, latency to paresis due to white matter lesions, and fractionation sensitivity. The 50% effect dose (EDso) for single dose irradiation at one week was 19.5 Gy, which is only lo%, but significantly (p < 0.05), lower than the EDg of about 21.5 Gy at 3 weeks and above. The latency to paresis was clearly influenced by the age at irradiation. The latency in the rats irradiated at 1 week was about 2 weeks, while for adult rats a latency of about 8 months was observed. The fractionation sensitivity for irradiation at 1 week was lower than the fractionation sensitivity of the adult rats; the (Y/B value at 1 week was estimated to be 4.5 Gy, while for the adult rats an (Y/B value of 1.8 Gy was found. As a consequence, the observed small difference in tolerance to single doses between 1 week-old and adult rats is further enhanced after fractionated irradiation. During prolonged irradiation treatments this decreased tolerance may be compensated by a higher proliferation rate in the immature central nervous system. The results of the present experiments indicate that, for a single tissue and endpoint, paresis due to white matter lesions in the rat cervical spinal cord, the latency to expression of damage and the fractionation sensitivity clearly change with age at irradiation. Age, Spinal cord, Radiation tolerance, Radiation myelopathy, Fractionation, Late effects, Development. INTRODUCTION Many developing tissues are more vulnerable to the effects of radiation than tissues of adult animals, presumably because of the more active proliferation. Age dependent differences in radiation response have been described for rat skin (9) mouse kidney (4), pig kidney (16), and guinea- pig spinal cord (11). However, very little is known about the fractionation sensitivity of the developing tissues. Be- cause it may be expected that not only tolerance, but also fractionation sensitivity is decreased in actively prolifer- ating tissues, we investigated single dose tolerance and fractionation sensitivity of the cervical spinal cord of 7 day-old and adult rats. METHODS AND MATERIALS Animals Male and female Wistar rats (CPB/WU) were used in this study at an age of 7 days and female rats of the same strain at 15- 18 weeks (adult rats). The rats were housed in macrolon cages and provided with water and food ad libitum. The 7 day-old rats were housed 10 in a cage with one adult foster-mother until weaning at the age of 3 weeks. Irradiations Prior to irradiation, the animals were anesthetized with Ethrane inhalation (2). Positioning was facilitated using a lucite fixation setup, enabling us to irradiate six animals simultaneously. All irradiations were performed with 4 MV photons on a linear accelerator at a focus-spinal cord distance of 100 cm. Dosimetry was performed at the level of the spinal cord, with appropriate sized phantom mea- surements as well as TLD measurements in situ in killed animals. In the 1 week-old rats exposure of a 8 mm seg- ment of the cervical and upper thoracic spinal cord (Cl through T4-T5) was carried out at a dose-rate of 2.1 Gy/ min. The adult rats were irradiated on a 18 mm cervical Reprint requests to: A. J. van der Kogel, Ph.D., Institute of Radiotherapy, University of Nijmegen, P.O. Box 9 101, 6500 HB Nijmegen, The Netherlands. Acknowledgements-The authors wish to thank W. F. M. Brou- wer for physics support, T. Oostendorp for expert technical as- 505 sistance and J. Koedam and coworkers of the Central Animal Laboratory for excellent collaboration. This work was supported by grant NUKC 88-2 from the Dutch Cancer Society. Accepted for publication 2 1 April 1992.