Biological Effects of Tritium Radiation Quantitatively Estimated Using Mouse Fetal Cell Damage

• Project/Area Number: 08680539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nuclear fusion studies
• Research Institution: Toho University School of Medicine
• Principal Investigator: YAMADA Takeshi Toho University School of Medicine, Department of Biology, Professor, 医学部, 教授 (30166714)
• Co-Investigator(Kenkyū-buntansha): 大山 ハルミ 放送医療技術研究所, 障害基盤研究部, 特別研究員 (70160645)
• Project Period (FY): 1996 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 1998: ¥300,000 (Direct Cost: ¥300,000); Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
• Keywords: Radiation effects / beta-rays / Mice / Fetal development / Role of apoptosis / RBE / B線 / RBF / 放射線

Research Abstract

Effects of beta-radiation from 4 kinds of organically bound tritium compounds (OBTs) including methyl-^3H-thymidine were investigated on cultured mouse embryonic mid brain cells (MBC). The relative biological effectiveness (RBE) values, ranging from 4.6 to 8.7, of beta ray from OBTs were obtained when compared with X-irradiation at their ID5Os (50 % inhibiton dose) on the inhibition of cell proliferation and differentiation, and on the decrease of DNA and protein contents of the cultures. Doses as low as 5 cGy from a mixed exposure resulted in detectable inhibitory effects.
Induction of apoptosis by tritium exposure was investigated in both MBC and brain sections of embryos and of newborns in mice. In the cultures of MBC, addition of methyl-^3H-thymidine (^3H-TdR) (21 kBq ml^<-1>) and tritiated water (HTO) (5.616 MBq ml^<-1>) induced late appearances and low percentages of apoptosis when compared to X-irradiation at the ID50 dose. The pregnant mice were given an intraperitoneal injection of HTO at the concentration of 481.8 kBq g^<-1> of body weight on gestation day 12.5, by which treatment behavioral changes in the offspring occurred. Increased apoptotic cells were observed in the neural tube of embryos from 1 day after the injection to 1 week postnatal age. Apoptosis induced by X-rays appeared 2 h after irradiation, with a peak at 4 h. Increase of apoptotic cells was also found in the brain cortexes of newborns. The percentage of apoptosis in the brain was higher in the prenatal HTO exposed mice than in the prenatal X-irradiated mice. Possible mechanisms on apoptosis and its relation to the higher relative biological effectiveness (RBE) value of tritium beta-rays are discussed.

Research Products

• [Publications] Wang B, Yamada T.et al.: "Effects of β radiation from organically bound tritium on the cultured mouse embryonic mid brain cells." Health Physics. 71. 913-919 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wang B, Yamada T.et al.: "Induction of apoptosis in clutured midbrain cells from embyronic mice." Radiation Res.143. 304-308 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wang B, Yamada T.et al.: "Radioadaptation in embryogenesis : I.Dose and timing for reducing of prenatal death and congenital malformation during the late period of Organogenesis." Radiat.Res.150. 120-122 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wang B, Yamada T.et al.: "Radiation-Induced Apoptosis Responsible for Limb Teratogenesis of Embryonic Mice" Radiat.Res.151. 63-68 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wang B, Yamada T.et al.: "Radiation-induced apoptosis in the mid brain cells in embryonic mice." Health Physics. (印刷中). (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wang B,Watanabe K,Yamada T,Shima A.: "Effects of beta radiation from organically bound tritium on the cultured mouse embryonic mid brain cells" Health Physics. 71. 913-919 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wang B,Watanabe K,Yamada T,Shima A.: "Induction of apoptosis in cultured midbrain cells from embyronic mice." Radiation Res. 143. 304-308 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shiokawa, D., Ohyama, H., Yamada, T.and Tanuma, S.: "Purification and properties of DNase gamma from apoptotic rat thymocytes." Biochem.J.326. 675-681 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujita, K., Ohyama, H.and Yamada, T.: "Quantitative comparison of in situ methods for detecting apoptosis induced by X-ray irradiation in mouse thymus." Histochem.J.29. 823-830 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hama-Inaba, H., Wang, B., Mori, M., Matsushima, T., Saitoh, T., Takusagawa, M., Yamasa, T., Muto, M.and Ohyama, H.: "Radiosensitive murine thymoma cell line 3SB.Characterization of its apoptosis resistant variants induced by repeated X-irradiation." Mutat.Res.403. 85-94 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wang, B., Ohyama, H., Nose, T., Itsukaichi, H., Nakajima, T., Yukawa, O., Odaka, T., Tanaka, K., Kojima, E., Yamada, T., and Hayata, I.: "Radioadaptation in embryogenesis : I.Dose and timing for reducing of prenatal death and congenital malformation during the late period of Organogenesis." Radiat.Res.150. 120-122 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wang, B., Fujita, K., Ohhira, C., Watanabe, K., Odaka, T., Mitani, H., Hayata, I., Ohyama, H., Yamada, T.and Shima, A.: "Radiation-Induced Apoptosis Responsible for Limb Teratogenesis of Embryonic Mice." Radiat.Res.151. 63-68 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wang, B., Takeda, H., Gao, W., Zhou, X., Odaka, T., Ohyama, H., Yamada, T., Hayata, I.: "Radiation-induced apoptosis in the mid brain cells in embryonic mice." Health Physics. (in press). (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wang B, Yamada T.et al.: "Effects of β radiation from organically bound tritium on the cultured mouse embryonic mid brain cells." Health Physics. 71. 913-919 (1996)
• [Publications] Wang B, Yamada T.et al.: "Induction of apoptosis in cultured midbrain cells from embyronic mice." Radiation Res.143. 304-308 (1997)
• [Publications] Wang B, Yamada T.et al.: "Radioadaptation in embryogenesis : I.Dose and timing for reducing of prenatal death and congenital malformation during the late period of Organogenesis." Radiat.Res.150. 120-122 (1998)
• [Publications] Wang B, Yamada T.et al.: "Radiation-Induced Apoptosis Responsible for Limb Teratogenesis of Embryonic Mice" Radiat.Res.151. 63-68 (1999)
• [Publications] Wang B, Yamada T.et al.: "Radiation-induced apoptosis in the mid brain cells in embryonic mice." Health Physics. (印刷中). (1999)
• [Publications] Wang,B., Yamada,T. et al.: "Effects of β radiation from organically bound tritium on the cultured mouse embryonic mid brain cells" Health Physics. 71. 915-919 (1996)
• [Publications] Wang,B., Yamada,T. et al.: "Induction of apoptosis in cultured midbrain cells from embyronic mice" Radiation Research. 143. 304-308 (1997)
• [Publications] Wang B,Yamada T,et al.: "Effects of UVC irradiation on the mouse embyonic cell culture with or without fluorescent light treatment" Mutation Research DNA repair. 362. 175-180