||γ-TDMG and Zn-yeast, Radiation Mitigators, Did Not Affect the Carbon-beam-induced Growth Inhibition of Xenograft Tumor on Mice
Anzai, Kazunori ,
Ueno, Megumi ,
Ken-ichiro, MatsumotoTakata, Jiro
Heavy ion radiotherapy has recently received increasing attention in the field of radiotherapy because heavy ion irradiation is more effective than other types of ionizing irradiation such as X-ray or γ-radiation. The carbon ion beam used in heavy ion irradiation releases a large amount of energy at the end of its range and enables the safe delivery of an effective dose of irradiation to tumors without damaging normal tissues. We have reported that γ-tocopherol-N,N-dimethylglycine ester (γ-TDMG)  and heat-treated zinc-yeast (Zn-yeast)  are potent radiation mitigators preventing bone marrow death of mice even when administered after whole-body irradiation of a near-lethal dose of 7.5 Gy X-rays. In the present study, at first we examined if γ-TDMG and Zn-yeast are also effective to prevent bone marrow death of C3H mice against carbon-beams (290 MeV, SOBP 6 cm). γ-TDMG (100 mg/kg) or Zn-yeast (100 mg/kg) suspended in 0.5% methyl cellulose solution was injected i.p. after whole-body carbon-beam irradiation on the mice. As a result, we found that both mitigators reduced the mortality of the mice when administered i.p. after whole-body irradiation of 6.0 Gy carbon-beams. Next, we examined if these mitigators affect the growth-control of xenograft tumors by carbon- beams. C3H mice were injected s.c. with RIF-1 cells at right thigh. When the tumors had reached a volume of 70-100 mm3, the mice were divided into four groups (carbon-beams ± and mitigators ± ). It was found that the local irradiation dose to appropriately inhibit the growth of the xenograft tumor is 8.0 Gy. The mitigators were administered to mice i.p immediately after irradiation. The tumor volume (V) was calculated as V (mm3) = length (mm) x width (mm)2/2. The observation was brought to an end when the tumors exceeded 1,000 mm3 in the volume or became severely necrotic.Both γ-TDMG and Zn-yeast did not reduce the inhibition effect of the carbon-beam treatment on the xenograft tumor growth. These findings suggest that the mitigators might be useful for the protection of normal tissues at the radiation therapy by carbon-beams.  K. Anzai et. al. (2014) J. Radiat. Res. 55, 67-74.  M. Ueno et. al. (2009) Radiat. Res. 172, 519-524.
15th International Congress of Radiation Research (ICRR 2015)