GUINEA-PIG SPINAL-CORD AS A MODEL FOR THE STUDY OF LATE RADIATION-INJURY AND REPAIR

Abstract

The risk of normal tissue damage imposes severe limitations on the radiotherapy of malignant tumours. The aim of this study was to examine the morphology of late radiation injury with special reference to microvasculature in the irradiated guinea pig spinal cord. Gamma radiation from a cobalt-60 source was used to irradiate the lumbar region of guinea pigs. A total dose of up to 94.5 Gy was given using 4.5 Gy fractions. Twenty such guinea pigs which survived more than 2 years post-irradiation were deeply anaesthetized and Mercox resin was perfused through the thoracic aorta. Ten minutes following perfusion, irradiated segments of the spinal cords were removed and either fixed in formalin for histology and morphometry or corroded in KOH for microvascular cast preparation. The latter were observed under the scanning electron microscope. All irradiated specimens showed multifocal white matter vacuolation. None of these spaces communicated with blood vessels. No such vacuolation was observed in grey matter. Glial cell counts in the irradiated white matter were reduced. Microvascular morphometry revealed 3.30% of the area was occupied by vasculature in the non-irradiated white matter. The corresponding value for irradiated white matter was 2.38% (p=0.003). No difference in the vascular area was noted in the non-irradiated grey matter (9.75%) and irradiated grey matter (10.36%; p=0.36) Microvascular casts did not reveal telangiectasia. However, irradiated specimens showed focal avascular regions. This was consistent with the light microscopic observation of focal degeneration and necrosis of irradiated white matter. These results suggest that late radiation injury in guinea pigs results primarily from damage to glial elements and the microvasculature is secondarily affected.