Vol. 2, 2017

Original research papers

Radiobiology

EFFECT OF N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST ON RADIATION-INDUCED GUT INJURIES IN MICE

Masatsugu Ohgami, Nobuhiko Takai, Masahiko Watanabe, Koichi Ando, Akiko Uzawa, Ryoichi Hirayama

Pages: 6-10

DOI: 10.21175/RadProc.2017.02

The intestinal crypt stem cells in gut have a high growth potential and radiosensitivity, it is dose-dependently reduced by heavy-ion irradiation and intestinal death occurs by arrest of epithelial cells supply in high dose area. The radiation to abdominal cancer, for example uterus and bladder, could give impairments not only on tumor, but also on gut nearby target. Therefore, the development of radioprotective agents for gut may contribute to more effective and less harmful heavy-ion therapy. N-methyl-D-aspartate receptor (NMDAR) is one of glutamate receptors and NMDAR antagonist has been reported to prevent the radiation-induced injuries in the central nervous system. Thus, we examined whether the peripheral NMDAR activation is a possible cause of gut injuries in mice irradiated with carbon-ion beam. We compared the dose-dependent change in the number of crypts after irradiation between treated MK-801 (0.1 mg/kg), a noncompetitive NMDAR antagonist, and untreated mice in order to confirm a MK-801 radioprotective effect on crypts. Compared with the sham group, the number of crypts in MK-801 group was significantly increased at 12.0 Gy or over. The radiolabeled [3H]MK-801 was intravenously injected with C3H female mice received 9 Gy whole body irradiation (290 MeV/u, 20 keV/μm). The significant increase was observed in [3H]MK-801 at 24 hr and 48 hr after irradiation, followed by decrease thereafter. These results suggest that intestinal NMDAR are most activated at 48 hr after carbon-ion irradiation. Thus, we suggested that radiation-induced gut injuries could be suppressed by NMDAR antagonists as radioprotective agents until 48 hr after carbon-ion exposure.
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