Γ-H2AX, 53BP1, Mre11, MDC1 As A Biomarker Of Low Dose Radiation

ObjectiveIn the field of radiation medicine and ionization radiation protection, there are the following indexes to forecast the radiation sensitivity of tumor cells and estimate the biological dose of people:（1） Chromosome distortion analysis, which is currently widely used as a golden standard. Although the analysis is accurate, the workload is big, and test cycle is long; （2） ESR analysis, whose dose range is wide, but materials are hard to get; （3） The changes of gene expression using molecular biology technology. In addition, in recent years, more and more people are concerned about other indexes as DNA damage proteins like histone y-H2AX, copy number variation, metabolomics studies, and some progress has been made. However, people know very little about the biological effects of low dose ionizing radiation, and the estimation methods of low dose ionizing radiation are not mature either. This study selects DNA repair proteins y-H2AX, MDC1,53BP1, Mre11 as main indexes. y-H2AX occurs on early stage of DNA Double-strand breaks （Double Strand Break, DSB）, and can raise MDC1 （Mediator of DNA damage checkpoint protein 1）,53BP1 （p53-binding protein 1）, Mrell （meiotic recombination 11 homolog A） into the injury site to get involved in DSB repair. This study attempts to explore the dose-response relationship on low dose levels, which might help the exploration of fast, efficient and accurate radiation biomarker in daily medical radiation.Materials and methods1、Analyze the foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of AHH-1 after being exposed to ⁶⁰Co γ rays on several time level （1 h,2 h,6 h,18 h）, and make the fitting dose-effect curves using statistical methods2、Analyze the foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of peripheral blood lymphocyte after being exposed to ⁶⁰ Co γ rays after 1 hour, and make the fitting dose-effect curve using statistical methodsResults1、Foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of AHH-1 after being exposed to ⁶⁰Co γ rays after 1 h and 2 h increases when the dose grows on and have a very good dose-effect relationship, which can be fitted to linear equations. R2 value is very high. Foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of AHH-1 after being exposed to ⁶⁰Co γ rays after 6 h and 18 h has nothing to do with the radiation and has no dose-effect relationship.2、Foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of AHH-1 after being exposed to ⁶⁰Co γ rays after 1 h and 2 h in the radiated groups above 25 mGy is higher than those of non-irradiated group with statistical difference （p<0.05）. The level of foci formation after 1 h is higher than that after 2 h, which suggests and decreasing trend with time. Foci formation of all those proteins after 6 h and 18h in irradiated group has no statistical difference3、Foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of peripheral blood lymphocyte after being exposed to ⁶⁰Co y rays after 1 h increases when the dose grows on and have a very good dose-effect relationship, which can be fitted to linear equations. R2 value is very high.Conclusion1. Foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of AHH-1 has a very good linear dose-effect relationship after being exposed to low dose radiation within 2h.2. Foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of AHH-1 decreases when time goes on and goes down to normal level after 6 hours.3. Foci formation of γ-H2AX, MDC1,53BP1 and Mrell protein of AHH-lhas a very good linear dose-effect relationship after being exposed to low dose radiation after 1 h.In summary, DNA damage protein γ-H2AX, MDC1,53BP1 and Mrell are basically equipped with the conditions to be low dose radiation biomarkers.