| Accurate and rapid radiation dose assessment has become increasingly important for the effective triage and medical management of population exposure to ionization radiation during the event of large-scale radiological accident.It is considered to be an important issue in radiation safety assessment,early risk warning and protection.How to find specific radiation-responsive genes has become one of the key scientific issues that should be solved urgently in radiation dose monitoring and radiation risk assessment.DNA damage response(DDR)is one of the most predominant molecular pathways induced by radiation exposure,and more importantly,DDR is evolutionarily conserved among different species.According to the conserved features of DDR,in this study,a novel method for screening new regulating genes involved in DDR based on plant genomes was established,and then radiation biomarkers screening and radiation dose prediction were carried out.The details are as follows:(1)First,in this study,a novel method was established for screening new regulating genes involved in DNA repair based on the plant genome.The results showed that a total of 16 novel human potential DNA repair genes were identified based on the Arabidopsis thaliana genome,in which 13 candidates,including ASF1A,ASF1B,CHAF1A,CHAF1B,DMC1,ERCC1,ESCO1,ESCO2,HLTF,MUS81,NAP1L1,SET and TTF2,were involved in the homologous recombination(HR)repair,and 3 candidates,including ATR,PARP1 and PARP2,were involved in the non-homologous end joining(NHEJ)repair.According to the literature research,three quarters candidate genes were confirmed to play key roles in the corresponding DNA repair pathways,suggesting the feasibility of the present method.We found that most of candidate genes expressions were changed significantly after radiation exposure by analyzing gene expression profiles,suggesting that the candidate genes may participate in the repair process of radiation-induced DNA damage.These result,indicated that the proposed method is effective in identifying the human potential DNA repair functional genes,and provides the potential targets for the development of radiation biomarkers.(2)And then,based on the above method,a novel method was further established for identifying human radiation-responsive biomarkers based on multiple plants genomes and predicting radiation dose.The results showed that 23 human specifically responsive genes to?-ray were finally obtained based on the 53 plant species genomes.Besides the known human specifically responsive genes to y-ray,a total of ten novel plant-based human specifically responsive genes to ?-ray,including ANKRD52,DOM3Z,NBN,ANKRD44,ATR,CCNA2,CCNB1,RAD54B,RAD54L and STIP1,were identified.And then,under high-and low-dose conditions,the gene expressions of the integrated human specifically responsive genes(including the novel and known genes)to ?-ray in the gene expression profiles of human peripheral blood cells after y-ray exposure were used to establish the multiple linear regression model for radiation dose prediction by the method of stepwise regression.The results showed that,the performances of multiple linear regression models established by the integrated human specifically responsive genes to y-ray was obviously superior to that of models established by the known human specifically responsive genes to ?-ray,which indicated that the specifically radiation-responsive genes selected in this study could be used as radiation biomarkers,and had good performance of radiation dose evaluation.In summary,methods for identifying human potential DDR-related genes based on plant genomes were established in this study,and a panel of human potential DNA repair and specifically radiation-responsive genes were identified by using these methods.Through biological function analysis and radiation dose modeling,we found that these potential genes could be used as radiation biomarkers for radiation dose evaluation.This study can provide novel research strategies for radiation biomarker screening and has potential applications in radiation dose assessment. |
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