Abstract
Intestinal crypt stem cells have a high growth potential and radiosensitivity. It is dose-dependently reduced by heavy-ion irradiation and intestinal death occurs by arrest of epithelial cell supply in high dose area. Radiation to abdominal cancer, for example uterus and bladder, could give impairments not only on tumor but also on gut nearby target. Therefore, we believe that gut protective agents contributes to more effective and less harmful heavy-ion therapy. NMDA receptor is one of excitatory amino acid receptors and NMDA antagonist has been reported to prevent the radiation induced injury. We have hypothesized that peripheral NMDA receptors correlates with events induced by radiation and conducted in vivo experiments to test the hypothesis.
The isotope-labeled [3H]MK-801 which is a noncompetitive NMDA antagonist was intravenously injected with C3H female mice and the biodistribution of MK-801 was investigated in time-dependent manner. Gut accumulation of MK-801 increased within 30 min after injection and reached maximum. MK-801 accumulation in gut after whole body irradiation of 9 Gy carbon-ion (290MeV/u, 20keV/µm) under unanesthesia were also examined. That increased until 24 hrs after irradiation and decreased afterward. These findings suggested that intestinal NMDA receptors are most activated at 24 hrs after carbon-ion irradiation and it is involved in gut impairments. Moreover, we compared the dose-dependent change of crypts after irradiation between treated with MK-801 and untreated mice in order to confirm a MK-801 protective effect on crypts.
