Research On Head-only Irradiation Of ¹²C Induced DNA Methylation Alterations In The Liver Of Mice

In this study, the male Balb/c and C57BL mice are selected as materials to study epigenetic mechanisms of space heavy ion radiation-induced bystander effect. The mice are exposed head-only to 40,200,2000 mGy of high energy radioactive ion beam 12C whose parameter is as follows, energy 165 MeV/n, the linear energy transfer 62.2 KeV/μm, dose rate 0.5 Gy/min, while the rest of the animal body is shielded. This study is intended to examine genomic DNA methylation change trends and characteristics with different time (1,6,12,24 h after irradiation) and doses in bystander organ liver of mice using methylation-sensitive amplification polymorphism method.The doses of 2000mGy and 200mGy head-only exposure result in a significant increase of genomic DNA methylation polymorphism in the bystander organ liver of male Balb/c and C57BL 1,6,12,24 h after irradiation. The top change is at 6 h after exposure and demethylation change rate is significantly higher than the methylation polymorphism rate. Demethylation polymorphism rate is highest separately at 1 h and 6 h after irradiation. The global DNA methylation changes tend to occur in the CG sites of genome sequence. The results illustrate that genomic methylation change of heavy ion radiation-induced bystander effect in liver can be obvious 1 h after radiation and achieve the maximum at 6 h. But these changes can recover gradually at 12 h.The paper further studies genomic DNA methylation polymorphism alterations in the bystander organ liver 6 h after head-only exposure to 40,200,2000 mGy of 12C heavy ion irradiation, are 1.19%±0.26%,1.44%±0.44%,1.23%±0.23% respectively as compared with control (0.50%±0.17%) (P<0.01). For further study, the unit dose contribution mutation rate are analyzed 6 h after 40,200,2000 mGy radiation, are 29.65%±6.60%,7.22%±2.22%,0.62%±0.12%. The finding is inconsistent with the linear no-threshold theory hypothesis that unit dose contribution mutation rate is the same. The result indicates that genomic methylation change in the bystander organ liver caused by less than 2000mGy of 12C high-energy heavy ion radiation is similar to non-linear no-threshold hypothesis of low doses biological effects.