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12 February 2025 Effects of Whole-Body Carbon-Ion Beam Irradiation on Bone Marrow Death in Mice and an Examination of Candidates for Protectors or Mitigators against Carbon-Ion-Beam-Induced Bone Marrow Death
Megumi Ueno, Shuichi Setoguchi, Kazuhisa Matsunaga, Ken-ichiro Matsumoto, Jiro Takata, Kazunori Anzai
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Abstract

The present study examined the effects of whole-body carbon-ion-beam irradiation on bone marrow death in mice and investigated whether compounds/materials, which were identified as efficient radio-protectors or mitigators against X-ray-radiation-induced bone marrow death, were also effective against the carbon-ion-beam-induced death of mice. Amifostine and cysteamine were used as radio-protectors and zinc-containing heat-killed yeast (Zn-yeast) and γ-tocopherol-N,N-dimethylglycine ester (γTDMG) as radio-mitigators. Amifostine or cysteamine was intraperitoneally administered in a single injection of 1.95 mmol/kg body weight 30 min before whole-body carbon-ion-beam irradiation. Zn-yeast or γTDMG was administered in a single intraperitoneal injection of 100 mg/kg body weight immediately after whole-body carbon-ion-beam irradiation. The absorbed dose dependence of the 30-day survival rate after carbon-ion-beam irradiation was analyzed. The biological effectiveness of carbon-ion-beam irradiation (LD50/30 = 5.54 Gy) was estimated as 1.2 relative to X-ray irradiation (LD50/30 = 6.62 Gy). The dose reduction factors (DRF) of amifostine, cysteamine, Zn-yeast, and γTDMG estimated for carbon-ion-beam irradiation were 1.75, 1.53, 1.16, and 1.15, respectively. Radioprotectors and -mitigators that were effective against photon irradiation also exhibited efficacy against carbon-ion-beam irradiation; however, the DRF for carbon-ion-beam irradiation was slightly smaller than that for photon irradiation. Based on the radio-protective effects of amifostine and cysteamine, the contribution of ROS/free radicals to carbon-ion-beam-induced bone marrow death was 70–90% to that of photon irradiation. Since the suppression of tumor growth by carbon-ion-beamirradiation was not inhibited by the treatment with γTDMG or Zn-yeast, both mitigators have potential as normal tissue-selective protectors in carbon-ion irradiation.

Megumi Ueno, Shuichi Setoguchi, Kazuhisa Matsunaga, Ken-ichiro Matsumoto, Jiro Takata, and Kazunori Anzai "Effects of Whole-Body Carbon-Ion Beam Irradiation on Bone Marrow Death in Mice and an Examination of Candidates for Protectors or Mitigators against Carbon-Ion-Beam-Induced Bone Marrow Death," Radiation Research 203(4), 246-256, (12 February 2025). https://doi.org/10.1667/RADE-23-00253.1
Received: 31 December 2023; Accepted: 2 February 2025; Published: 12 February 2025
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