Structural Alterations of the DNA in Cerebellar Neurons after Whole-Brain Irradiation

Male Sprague-Dawley rats weighing 260-280 g were whole-brain-irradiated with X-ray doses of 433, 867, 1083, 1300, 1516, and 1713 rad. Over the next 2.25 years rats were killed at various times, and the state of the DNA in their cerebellar neurons was examined by sedimentation through alkaline sucrose gradients in reorienting zonal rotors. The data were analyzed as the percentage of the sedimenting DNA with sedimentation coefficients greater than 300 S, an arbitrarily selected category of no defined molecular significance. The general pattern at all doses consisted first of a slow return to the unirradiated DNA state (≥4 weeks) that was relatively dose dependent. This was followed by an increase in the amount of DNA sedimenting >300 S; both the extent and time course of this increase appeared to be dose dependent. Finally, the DNA degraded at a relatively dose independent rate. There was little change in the neuronal DNA from unirradiated rats during this study. The data suggest that increases in the amount of fast-sedimenting DNA observed 30-80 weeks after low to moderate doses of whole-brain irradiation represent a type of DNA damage rather than repair and that this damage ultimately results in degradation of the neuronal DNA and death of the rat.