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More efficient induction of genotoxicity by high-LET Fe-particle radiation than low-LET X-ray radiation at low doses

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radiation Medicine and Protection 2023年第1期4卷 11-18页

作者： Bing Wang Takanori Katsube Kaoru Tanaka Yasuharu Ninomiya Hirokazu Hirakawa Cuihua Liu Kouichi Maruyama Masahiro Murakami Tetsuo Nakajima Akira Fujimori Mitsuru Nenoi National Institutes for Quantum Science and Technology Chiba263-8555Japan

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(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 fro

关键词： Fe-particle radiation Genotoxicity Genomic instability Micronucleated erythrocyte C57BL/6J mice

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ANTP-SMACN7 fusion peptide alone induced high linear energy transfer irradiation radiosensitization in non-small cell lung cancer cell lines

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Cancer Biology & Medicine 2022年第7期19卷 983-994页

作者： Yi Xie Bing Wang Liqing Du Yan Wang Chang Xu Hong Zhang Kaixue Wen Qiang Liu Takanori Katsube Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China Advanced Energy Science and Technology Guangdong Laboratory Huizhou 516029China National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and TechnologyChiba 263-8555Japan Institute of radiation Medicine Chinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Shanxi Bethune Hospital Shanxi Academy of Medical ScienceTaiyuan 030031China

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.

关键词： Fe-particle radiation carbon-particle radiation non-small cell lung cancer cells caspase radiosensitizer

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