Effects Of Radon Hot Spring On Cell Cycle And The Expression Of Cell Cycle Regulatory Proteins

[Background]Radon is radioactive gas widely existing in the natural environment.The radiation dose generated by internal radiation,which come from inhaling of radon and its daughters,accounts for about 54%(about 1.3 mSv)of the total natural radiation dose in the world.In 2005,the World Health Organization launched the International Indoor Radon Pollution Project(IRP)to assess the impact of radon and its daughters'exposure on the global disease burden(GDB),and ranked it as the preferred radio-nuclide,The radiation existed in Pingshan Hot Spring and jiangzha Hot Spring belongs to low-level radiation.Previous research group studied the cytogenetic parameters and miRNAs in the peripheral blood of residents around Pingshan Hot Spring and study on the expression of lung cancer related genes and miRNAs in the peripheral blood of residents around the jiangzha Hot Springs,and the study of chromosomal aberrations.The level of genetic and RNA levels in residents' peripheral blood has changed.Based on the previous research work of the research group,this study aims to further explore the changes in the peripheral blood lymphocyte cycle and protein levels in the residents around the radon hot springs.[Purpose]Based on the previous studies,this experiment explored the effects of long-term multiple radon hot spring exposures in two regions of Pingshan County.Hebei Province and jiangzha Township,Sichuan Province,on the changes of the peripheral blood lymphocyte cycle and CDK1,CDK2,CDK4,CDK6,CyclinD1,and CyclinE1 expression in the peripheral blood of residents;The changing levels of 8-OHdG and TrxR were detected,and the oxidative damage and anti-oxidation levels in the body were initially analyzed to explore the influence of radon hot springs on surrounding residents.[Method]A simple random sampling method was used to collect 46 residents around the hot springs in Pingshan County,and 39 residents in the control area were selected.Flow cytometry was used to detect the changes of cell cycle and the expression levels of the regulatory proteins CDK1,CDK2,CDK4,CDK6,CyclinDl,CyclinEl,Wee1,CDC25A respectively.ELISA was used to detect the 8-OHdG and TrxR levels in plasma.The test data were compared by t-test and Mann-Whitney U test to show the difference between the two groups.Multiple linear regression analysis was used to analyze the relationship among the differential expression of regulatory proteins,8-OHdG,and TrxR,and the exposure to radon.A simple random sampling method was used to collect 38 residents around the hot springs in the jiangzha Hot Spring,and 40 residents in the control area were selected.Flow cytometry was used to detect the proportion of lymphocyte cell cycle and the expression levels of the regulatory proteins CDK1,CDK2,CDK4,CDK6,CyclinA2,CyclinD1,and CyclinEl.RT-PCR was used to detect that expression of let-7a,miR-16 and miR-34a in plasma.ELISA was used to detect the 8-OHdG and TrxR levels in plasma.The test data were compared by t-test and Mann-Whitney U test to show the difference between the two groups.Linear regression analysis was used to examine the relationship among the differential expression of regulatory proteins,miRNAs,8-OHdG,TrxR,and the exposure to radon.[Result]1.Results of Pingshan hot spring(1)Compared with the control group,the proportion of lymphocytes in G0/G1 phase decreased by an average of 0.38%,and the proportion of lymphocytes in S phase increased by an average of 0.39%.The difference in the percentage of lymphocytes in the two groups was significant.There was statistical significance(t=2.250,-2.382,P<0.05).(2)Compared with the control group,the expression level of CDK6 was significantly down-regulated(t=10.737,P<0.05),which was 0.49 times compared to the control group;the expression levels of CDK1 and CyclinEl were significantly down-regulated(Z =-5.091,-4.564,P<0.05),which was 0.82 times and 0.67 times compared to the control group respectively.(3)Compared with the control group,the plasma levels of 8-OHdG in the peripheral blood of the residents in the radon group were significantly lower,and the TrxR levels were significantly higher(Z=-3.550,-2.394,P<0.05),which was 0.62 times and 1.37 times,respectively,compared to the control group.2.Results of Jiangzha Hot Spring(1)Compared with the control,the proportion of lymphocytes in the G0/G1 phase of the radon group increased by an average of 0.42%,and the proportion of S phase lymphocytes decreased by an average of 0.38%.The difference in the percentage of lymphocytes in the two groups was significant.There was statistical significance(t=-2.089,2.037,P<0.05).(2)Compared with the control group,the expression levels of CDK2 and CDK4 in the radon group were significantly down-regulated(t =-4.481,-2.834,P<0.05),which was 0.80 and 0.87 times respectively compared to the control group;The expression levels of CyclinA2 and CyclinDl were down-regulated while the expression level of CDK6 was up-regulated(Z =-2.549,-4.087,-3.34,P<0.05),which were 0.75 times,0.92 times and 1.13 times,respectively,higher compared to the control group.(3)Compared with the control group,the relative expression levels of miR-16 and miR-34a in the radon group increased significantly(Z =-2.844.-2.504.P<0.05),which were 2.31 and 2.20 times respectively compared to the control group.(4)Compared with the control group,plasma 8-OHdG levels in the peripheral blood of radon group were significantly lower while TrxR levels were significantly higher(Z =-3.316,-3.773,P<0.05),which were 0.57 and 2.33 times respectively that of the control group.[Conclusion]The cell cycle of peripheral blood lymphocyte cycle changes in residents around radon hot springs.The expression of cell cycle regulatory proteins also changed accordingly.The change of 8-OHdG and TrxR levels in the plasma of the residents around the hot springs in both places showed antioxidants level increased and oxidation level decreased.