A multidisciplinary challenge to assess the next-generation risks of low-dose-rate long-term gamma-ray exposure by whole-genome sequencing in the mouse model

To assess the biological risks of low-dose/low-dose-rate long-time radiation exposure, we have been conducting the multigenerational accumulation of de-novo mutations. We have succeeded in detecting spontaneous and radiation-induced mutations in the control and exposed mice, respectively, by using the whole-genome sequencing (WGS) technology. We have already identified over 4000 de-novo mutations in a total of 42 offspring mice compared to the original common pair of mice. It took less than 2 years from the first mating of the original pair to the completion of WGS; thus, it is very quick and cost-effective compared to the specific-locus test which is one of the representative risk assessment methods. According to the number of detected mutations, the precision and statistical power to detect de-novo mutations are extremely higher than any conventional risk assessment methods in the mouse model. We have detected a significant increase in the 20 mGy day −1 –induced base substitutions, which is the lowest dose rate ever detected in radiation-induced base substitutions. The mouse mutagenesis model based on the WGS technology, therefore, should provide a powerful tool to the risk assessment system, particularly on the low-dose/low-dose-rate long radiation exposures.