Accumulation of Neuronal DNA Damage as an Early Covariate or Determinant of Death after Whole-Brain Irradiation

Abstract

The state of the DNA from cerebellar neurons of male Sprague-Dawley rats after whole-brain irradiation with 2000 rad of X rays was determined at various times by obtaining DNA sedimentation profiles using alkaline sucrose gradients in slow reorienting zonal rotors. It took more than 4 weeks after irradiation for the neuronal DNA distributions to return to those obtained from the unirradiated controls. At 7 weeks, the DNA from irradiated neurons sedimented more rapidly than that from unirradiated neurons. Accumulation of the neuronal DNA damage (degradation?) which led to slower sedimenting DNA species began by Week 10 and continued until the majority of the irradiated rats began to die at Week 20. We propose as a working hypothesis that the accumulation of neuronal DNA damage initially observed 10 weeks after 2000 rad of whole-brain irradiation may reflect or cause changes in the central nervous system that later result in the death of the animal.