Relationship between dose and the latent period for radiation myelopathy in rats

A 1-cm segment of rat cervical spinal cord was irradiated (16-150 Gy) and the animals were followed for 16 months to determine the dose-response relationship for the latent period for radiation myelopathy. The latent period was found to be dependent on dose in the ED0 to ED100 dose range, independent of dose in the range ED100 to 1.5 times the ED100 dose and dependent on dose for doses more than 1.5 times the ED100 dose. Histologically, some vascular injury and demyelinization were observed in the irradiated cord segment of all paretic animals. In the first dose-dependent region there was a bimodal distribution of latent periods, suggesting two mechanisms for paralysis in this dose region. A hypothesis based on glial and vascular injury is presented which explains the triphasic dose-response relationship for the latent period. The 95% confidence limits for the dose location of both of the dose-dependent regions were less than 10% of the administered dose. Therefore, if used correctly, the latent period as an end point should be able to be used to detect dose-modifying parameters (i.e. RBE and OER) that are greater than 20%.