Early Effects of PRS-Irradiation for 9L Gliosarcoma: Characterization of Interphase Cell Death

Abstract
We characterized the interphase cell death of 9L gliosarcoma after high-dose-rate, low-energy photon irradiation using the Photon Radiosurgery System (PRS), a novel device for interstitial radiotherapy. Within 24 hours after irradiation with a dose of 18 Gray, 22.0 % of cells underwent metabolic cell death, whereas dead cells in controls stayed less than 5.0 % (p < 0.005). In the majority of sensitive cells, loss of membrane integrity preceded the lethal morphological changes. The response was dose-dependent over the range of 9 - 18 Gray, but saturation was obtained over 18 Gray. On the other hand, a significant (p < 0.01) increase in the number of TUNEL-positive cells with apoptotic morphology was detected 6 - 24 hours after irradiation, but the fraction remained 1.9 - 2.1 % of the population and was independent of the doses between 9 and 25 Gray. Apoptotic cells were rarely observed in the control cells (0.3 - 0.6 %). Our data indicate that single high-dose irradiation induces both necrotic and apoptotic interphase cell death in 9L gliosarcoma, but rapid cell death mostly occurs through the non-apoptotic pathway.