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

研究了甲基-^ 3h -胸腺嘧啶等4种有机结合氚化合物（OBTs）的β辐射对培养小鼠胚胎中脑细胞（MBC）的影响。与50%抑制剂量下的x射线照射相比，OBTs β射线对细胞增殖和分化的抑制作用以及培养物DNA和蛋白质含量的降低作用的相对生物有效性（RBE）值在4.6 ~ 8.7之间。混合照射低至5 gy的剂量可产生可检测到的抑制效应。研究了氚暴露在小鼠胚胎和新生儿的MBC和脑切片中诱导细胞凋亡的作用。在MBC培养中，与ID50剂量的x射线照射相比，添加甲基-^ 3h -胸腺嘧啶（^3H-TdR） （21 kBq ml^<-1>）和氚化水（5.616 MBq ml^<-1>）可导致晚出现和低凋亡百分比。妊娠第12.5天，给孕鼠腹腔注射浓度为481.8 kBq g^<-1>体重的HTO，使子代行为发生改变。注射后1天至出生后1周，胚胎神经管中凋亡细胞增多。x射线诱导的凋亡在照射后2 h出现，在照射后4 h出现凋亡高峰。新生儿大脑皮层凋亡细胞也有所增加。产前HTO暴露小鼠脑细胞凋亡比例高于产前x射线照射小鼠。讨论了可能的细胞凋亡机制及其与氚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.