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

研究了4种有机结合氚化合物(OBTs)对体外培养的小鼠胚胎中脑细胞(MBC)的辐射效应。在抑制细胞增殖和分化、降低细胞DNA和蛋白质含量方面，获得了来自OBTS的β射线的相对生物学效应(RBE)值，范围为4.6~8.7。低至5cGy剂量的混合照射可导致可检测到的抑制效应。研究了氚暴露对小鼠胚胎和新生儿的单核细胞和脑组织切片中细胞凋亡的诱导作用。在单个核细胞的培养中，加入~1H-TdR(21kBq·ml~(-1))和氚水(5.616 mBq·ml~(-1))诱导的细胞出现较晚，细胞凋亡率也较低。孕鼠于妊娠第12.5d以481.8 kBq·g~(-1)·g~(-1)体重的剂量腹腔注射HTO，观察仔鼠的行为变化。胚胎神经管内的凋亡细胞在注射后1d至出生后1周龄明显增多。X射线诱导的细胞凋亡在照射后2 h开始出现，4h达高峰，新生儿大脑皮层中的凋亡细胞也明显增多。胎儿期HTO暴露组小鼠脑组织细胞凋亡率高于孕期X射线照射组。讨论了细胞凋亡的可能机制及其与氚β射线较高的相对生物效应(RBE)值的关系。

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.