Analysis of tissue-specific mutations induced by radiation in HITEC mice

据认为，突变会导致各种疾病，包括畸形和癌症。然而，体内突变与疾病之间的关系很难从体外实验中找到，因此，我们使用转基因小鼠研究了体内辐射诱导的突变。我们使用被称为HITEC(体内超敏致癌性试验)的rpsL转基因小鼠，研究了睾丸、脾、肝脏、脑和胸腺中突变频率的差异。转基因小鼠系统对于研究辐射诱发的小鼠体内各种器官的体细胞突变是非常有用的。我们利用HITEC和p53(-/-)-HITEC小鼠研究了辐射诱发突变的组织特异性差异突变频率和突变诱导动力学。小鼠接受5Gy137&gt；Csγ射线全身照射，30、60、120和180天后处死动物。然后摘除每只小鼠的脑、胸腺、肝脏、脾和睾丸。辐射后不同器官的突变频率随时间的变化规律不同。在HITEC小鼠中，观察到的自发突变频率为：睾丸5×10；-5&gt；，脑8×10；-5&gt；，脾1.5×10；-4&gt；，肝脏6×10；-5&gt；当在照射后30-60天测量时，大脑的突变频率比对照水平高2-3倍，然后转向自发频率。睾丸自发突变率和辐射诱变率显著低于其他器官。在p53(-/-)-HITEC小鼠中，没有发现突变在任何器官中积累，因此，带有rpsL转基因的突变检测系统灵敏度较低，但对于检测辐射后雄性生殖细胞的基因突变是有用的。

It is thought that mutations cause various disorders including malformations and cancers. However, relation between mutations and disorders in vivo is difficult to find from in vitro experiments.Therefore, we have studied mutations induced in vivo by radiation with use of a transgenic mouse. We investigated difference in mutation frequencies in the testis, spleen, liver, brain and thymus using the rpsL transgenic mice so called HITEC (Hypersensitive In Vivo Test of Carcinogenisity). Transgenic mouse systems are very useful for the study of in vivo somatic mutations induced by radiations in various mouse organs. We investigated tissue-specific differences of radiation-induced mutagenesis in the mutant frequencies and the kinetics of mutant induction by using the HITEC and p53 (-/-)-HITEC mice. The mice were exposed to a whole-body dose of 5 Gy of ^<137>Cs Gamma-rays, and animals were killed 30, 60, 120 and 180 days later. Then the brain, thymus, liver, spleen, testes of each mouse were removed.Intriguingly, the pattern of change in the mutation frequency with time after irradiation varied for the different organs. In HITEC mice, spontaneous mutation frequencies observed were 5×10^<-5> for testis, 8×10^<-5> for brain, 1.5×10^<-4> for spleen and 6×10^<-5> for liver. When measured 30 to 60 days after irradiation, the mutation frequencies were 2 to 3-fold higher than the control level for the brain and then turned to the spontaneous rate. The frequencies of spontaneous and radiation-induced mutation in the testis were significantly lower than that in other organs. In p53(-/-)-HITEC mice, there were no findings that the accumulation of mutations in any organs.Therefore, the mutation assay system with the rpsL transgene is low in sensitivity but useful for detection of gene mutations in male germ cells after irradiation.