Objective:To understand differential effects on induction of genotoxicity and genomic instability(GI)by high-LET particle radiation and low-LET photon radiation,based on ground-based experiments using total body irrad...Objective:To understand differential effects on induction of genotoxicity and genomic instability(GI)by high-LET particle radiation and low-LET photon radiation,based on ground-based experiments using total body irradiation(TBI)of mice with Fe-particle radiation and X-ray radiation.Methods:TBI was delivered to C57BL/6J Jms strain female mice of 8 weeks old at a dose ranging from 0.1 to 3.0 Gy of Fe-particle radiation or at a dose ranging from 0.1 to 5.0 Gy of X-ray radiation.Induction of genotoxicity and GI by TBI was determined respectively at 1 and 2 months after exposure using frequency of micronuclei in bone marrow erythrocytes as the endpoint.Inhibition of bone marrow cell proliferation by TBI was measured as reduced erythropoiesis.Physiological conditions were also investigated.Results:TBI,regardless of the type of radiation,caused statistically significant increase in genotoxicity at 1 month after exposure,but did not induce GI at 2 months after exposure even at higher doses(>1.0 Gy).The doseresponse curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7798 t 1.7889x–0.5978x^(2)(R^(2)=0.8109)and y=0.7421 t 1.3792x–0.2588 x^(2)(R^(2)=0.8081),respectively.The dose-response curve for the frequency of micronucleated normochromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7191 t 1.4545x–0.4978x^(2)(R^(2)=0.7047)and y=0.658 t 1.344x–0.2531x^(2)(R^(2)=0.7853),respectively.In general,high-LET Fe-particle radiation was more efficient in inducing genotoxicity than low-LET X-ray radiation at lower doses(<0.5 Gy).Conclusions:These results further confirm that exposure to TBI,even at higher doses and regardless the type of radiation,does not induce GI in C57BL/6J strain mice measured as increased micronuclei in bone marrow erythrocytes.These findings indicate that radiation-induced GI is mouse strain dependent and suggest that more comprehensive studies should be done to explore the late health consequences from exposure to high-LET radiation at low doses.展开更多
Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and F...Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and Fe particle irradiation.Methods:The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells.A549 and NCI-H460 cells,human non-small cell lung cancer(NSCLC)cell lines,were irradiated with X-ray or high linear energy transfer(LET)irradiation with or without ANTP-SMACN7 treatment.Cellular survival,apoptosis,and protein expression were studied by colony formation assays,flow cytometry,and western blot analyses,respectively.Results:ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization.High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis(P<0.05).Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9.Conclusions:Regarding pharmaceutical radiosensitization,these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.展开更多
基金This research was financially supported in part by the Ministry of Education,Culture,Sports,Science and Technology(MEXT)Grant-in-Aid for Scientific Research on Innovative Areas,Grant Number 15H05935“Living in Space”and Research Project Grants(22B-258 and 14J-286)with Heavy Ions at HIMAC,QST,Japan.
文摘Objective:To understand differential effects on induction of genotoxicity and genomic instability(GI)by high-LET particle radiation and low-LET photon radiation,based on ground-based experiments using total body irradiation(TBI)of mice with Fe-particle radiation and X-ray radiation.Methods:TBI was delivered to C57BL/6J Jms strain female mice of 8 weeks old at a dose ranging from 0.1 to 3.0 Gy of Fe-particle radiation or at a dose ranging from 0.1 to 5.0 Gy of X-ray radiation.Induction of genotoxicity and GI by TBI was determined respectively at 1 and 2 months after exposure using frequency of micronuclei in bone marrow erythrocytes as the endpoint.Inhibition of bone marrow cell proliferation by TBI was measured as reduced erythropoiesis.Physiological conditions were also investigated.Results:TBI,regardless of the type of radiation,caused statistically significant increase in genotoxicity at 1 month after exposure,but did not induce GI at 2 months after exposure even at higher doses(>1.0 Gy).The doseresponse curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7798 t 1.7889x–0.5978x^(2)(R^(2)=0.8109)and y=0.7421 t 1.3792x–0.2588 x^(2)(R^(2)=0.8081),respectively.The dose-response curve for the frequency of micronucleated normochromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y=0.7191 t 1.4545x–0.4978x^(2)(R^(2)=0.7047)and y=0.658 t 1.344x–0.2531x^(2)(R^(2)=0.7853),respectively.In general,high-LET Fe-particle radiation was more efficient in inducing genotoxicity than low-LET X-ray radiation at lower doses(<0.5 Gy).Conclusions:These results further confirm that exposure to TBI,even at higher doses and regardless the type of radiation,does not induce GI in C57BL/6J strain mice measured as increased micronuclei in bone marrow erythrocytes.These findings indicate that radiation-induced GI is mouse strain dependent and suggest that more comprehensive studies should be done to explore the late health consequences from exposure to high-LET radiation at low doses.
基金supported by grants from the National Key R&D Program of China(Grant Nos.2018YFE0205100 and 2018YFE0205101)the National Natural Science Foundation of China(Grant Nos.11605260 and 31670859)+4 种基金the Key Research and Development Projects of Shanxi Province(Grant No.201903D321115)the Science and Technology Talent Project in Lanzhou(Grant No.2018-RC-66)the Science and Technology Project of Chengguan District of Lanzhou(Grant No.2020RCCX0038)the CAMS Innovation Fund for Medical Science(Grant No.2017-I2M-1-016)the Ministry of Education,Culture,Sports,and Science Technology Grantin-Aid for Scientific Research on Innovative Areas with Heavy Ions at NIRS-HIMAC,Japan[Grant Nos.JP15K21745,15H05944,and 15H05935(Living in Space),and Research Project Grant(14J313)].
文摘Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and Fe particle irradiation.Methods:The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells.A549 and NCI-H460 cells,human non-small cell lung cancer(NSCLC)cell lines,were irradiated with X-ray or high linear energy transfer(LET)irradiation with or without ANTP-SMACN7 treatment.Cellular survival,apoptosis,and protein expression were studied by colony formation assays,flow cytometry,and western blot analyses,respectively.Results:ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization.High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis(P<0.05).Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9.Conclusions:Regarding pharmaceutical radiosensitization,these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.
