||Mouse Model for the Biodosimetry Using Quantification of mRNA for DNA-damage Induced Genes in Peripheral White Blood Cells
Tanaka, Izumi ,
Yakumaru, Haruko ,
Tanaka, Mika ,
Yokochi, KazukoIshihara, Hiroshi
Biodosimetry by the measurement of chromosomal damage in lymphocyte has been established. Although the principle is useful to estimate high-dose exposure, expansion of the method to estimate low-dose exposure is difficult. We aimed to develop a biodosimetric method that is suitable for low-dose (around 100 mGy) radiation exosure, and focused on the quantification of RNA in white blood cells. For the future application of the methodology to human blood, basic knowledges were obtained using mouse model. We previously reported increase in the levels of mRNAs for DNA damage-induced (DDI) genes in peripheral blood from whole-body x-irradiated mice (JRR 51, 265-275, 2010). The DDI genes are known to be expressed in radiation-sensitive proliferating cell which is slightly contained in peripheral blood, and it is expected that the relative rates of the level of DDI gene expression per the proliferating cells would show dose-dependency that is necessary for biodosimetry. When bax and puma mRNAs were chose as indexes of DDI gene expression level and c-myc mRNA was used as an index of proliferating cell number, the values of bax/myc and puma/myc rates in peripheral blood were kept low level without significant change among all the mice. When blood were isolated from mice 2h after whole-body x-irradiation in the various doses from 25 to 500mGy, these values of relative rates were increased in exposed dose-dependent manner. Similar dose-dependent increase was also observed in blood samples isolated from 4h after irradiation, but all the values elevated as compared with blood isolated from 2h after irradiation. Thus, records of blood sampling time and predicted irradiation time are essential in this model. No significant change was observed in these values of relative rates among different irradiation experiments using any production batches of mice. This mouse model can be useful not only to study radiation effect in vivo but also to elucidate basic knowledge that is necessary to expand the biodosimetric methodology to human.
15th International Congress of Radiation Research