Physiological, genomic effects in descendant mice after the every generational low dose-rate internal ¹³⁷Cs radiation exposure

To investigate the transgenerational effects of chronic low dose-rate internal radiation exposure after the Chernobyl and Fukushima nuclear power plant accident, every generations of mice were maintained in the radioisotope facility with free access to drinking water containing ¹³⁷CsCl (0 and 100 Bq/ml), as a simulation experiment of the internal exposure. Two mouse pairs were selected from among A/J mice strain littermates bred in the radioisotope facility. One pair was assigned to the control group and bred while offered drinking water ad libitum; the other pair was administered a low-dose internal radiation exposure of ¹³⁷CsCl water (100 Bq/mL). Harvested offspring from both pairings were sibling-mated for more than 10 generations, corresponding to a human generation turnover of approximately 300 years. Mice of the tenth generation (F₁₀) were assessed gamma-H2AX foci in hepatic cell, micro nuclei test, chromosome aberration analysis, tumorigenicity of lung, oxidative stress, metabolomic analysis in heart, and the structure abnormality of the myocardium with the electron microscope. Suppression of the tumor growth, increasing of the gamma-H2AX focus number, tendency to swelling of myocardium mitochondria, and the metabolite of oxidative stress were observed in ¹³⁷Cs drinking mice, however, no significant difference was observed in the analyses of micro nuclei test, chromosome aberration, and tumor incidence. Therefore we performed all mouse genome sequences of the mouse (15th generation) to detect accumulated genomic mutations. Because small genomic mutations could occur, be inherited, and accumulate in each successive generation in non-coding genomic regions (introns and intergenic) and have no effect on survival, we compared levels of accumulated base mutations between the offspring exposed to continuous low-dose radiation and control mice of the same generation that started from a littermate mouse. This work was supported by JSPS. (author)