| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
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.
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