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

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 irradiation-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. Radio-protectors 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% of that to photon irradiation. Since the suppression of tumor growth by carbon-ion beam irradiation was not inhibited by the treatment with γTDMG or Zn-yeast, both mitigators have potential as normal tissue-selective protectors in carbon-ion radiation therapy.journal articl