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Objective:To obtain the relative biological effectiveness (RBE) of DNA double strand breaks (DSB) clusters by tracing the mechanism of radiated DNA damage, and explore the relationship among the biological effectiveness of DNA damage, chromosomal aberrations and germ cell death.Methods:Taking low-energy electrons, protons, and α particles as the research objects, this study simulated the process that cell nuclei were exposed to particle radiation using a radiation-related physicochemical model. On the ground of the DSB density-based spatial clustering of applications with noise (DBSCAN) algorithm, the DSB cluster classification method was improved to weaken the connection between the DSBs and the random distribution assumptions of energy depositions during the simulation. In this manner, the DSB clusters can be much closer to a non-random distribution. Furthermore, this study obtained the yields of DSB clusters and proposed a method to calculate the RBE values of DSB clusters.Results:The calculated RBE value (12.29) of DSB clusters of 2 MeV α particles was similar to the experimental RBE values of chromosomal fragments (15.3±5.9) and cell survival (14.7±5.1).Conclusions:After high-LET ionizing radiation, unlike the single DSB, the RBE of DSB clusters was similar to that of chromosomal aberration and cell survival.
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Objective:To calculate the relative biological effectiveness (RBE) value of the released low-energy electrons in gadolinium neutron capture therapy ( 157GdNCT) based on microdosimetry. Methods:The Monte Carlo (MC) code Geant4-DNA package was used to simulate the energy deposition distribution and microdosimetry parameters of low-energy electrons released during gadolinium neutron capture treatment in different sensitive target volumes and physical models on track structures. On this basis, RBE value was obtained based on the microdosimetry kinetic model (MKM).Results:The low-energy electron RBE value was highly variable in different sensitive target volumes and decreases with increasing sensitive target volumes. With 6-nm-diameter sensitive target as reference, RBE value was 1.77 for 6-nm diameter, 1.53 for 10 nm diameter with percentage difference 13%, and 1.40 for 15-nm diameter with percentage difference of 21%, respectively. The effect of different Geant4-DNA physical models on the RBE of low-energy electrons was small. Using the RBE value of 1.53 for physical model option2 as reference, the RBE values of option6 and option7 were 1.49 and 1.52, respectively, with the percentage differences of 2.6% and 0.6%, respectively.Conclusions:The RBE values of low energy electrons released by 157GdNCT in different sensitive target volumes and physical models were calculated by MKM to be 1.40-1.77.
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Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.
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Objective:To measure the microdosimetric spectrum of carbon ion beam and calculate the relative biological effect (RBE) distribution, so as to provide reference for radiotherapy microdosimetric research.Methods:A silicon on insulator (SOI) microdosimeter was used to measure the microdosimetric spectrum of 12C ion beam, at 260 MeV/u, provided by Lanzhou Heavy Ion Accelerator National Laboratory. The measured pulse amplitude spectrum was converted to obtain the dose distribution. The microdosimetric spectra and RBE values at different polymethyl methacrylate depths were measured by the combination of different thickness PMMA. Results:The microdosimetric spectra of 12C ion beam at 260 MeV/u were measured at different PMMA depths, and the relationship between dose line energy yD and RBE and different PMMA depths was also obtained. The measurement result showed that the RBE value reached a peak of 2.6 at the PMMA depth of 116.5 mm, and decreased rapidly after the Bragg peak. However, the RBE value was still 1.3 at the trailing point, which was about twice as much as the entrance of the flat zone. Conclusions:This paper provides basic data for carbon ion beam microdosimetric spectroscopy through measurement. The RBE value of 12C ion beam gradually rises and reaches a peak with the increase of PMMA depth. After the Bragg peak position, it drops rapidly, but the biological effect at the tail cannot be ignored. At the same time, it reflects the dose fraction caused by different line energy intervals, and provides a reference for assessing the risk of heavy ion therapy for secondary cancer.
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PURPOSE: Although static magnetic fields (SMFs) have been used in dental prostheses and osseointegrated implants, their biological effects on osteoblastic and cementoblastic differentiation in cells involved in periodontal regeneration remain unknown. This study was undertaken to investigate the effects of SMFs (15 mT) on the osteoblastic and cementoblastic differentiation of human osteoblasts, periodontal ligament cells (PDLCs), and cementoblasts, and to explore the possible mechanisms underlying these effects. METHODS: Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, mineralized nodule formation based on Alizarin red staining, calcium content, and the expression of marker mRNAs assessed by reverse transcription polymerase chain reaction (RT-PCR). Signaling pathways were analyzed by western blotting and immunocytochemistry. RESULTS: The activities of the early marker ALP and the late markers matrix mineralization and calcium content, as well as osteoblast- and cementoblast-specific gene expression in osteoblasts, PDLCs, and cementoblasts were enhanced. SMFs upregulated the expression of Wnt proteins, and increased the phosphorylation of glycogen synthase kinase-3β (GSK-3β) and total β-catenin protein expression. Furthermore, p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways were activated. CONCLUSIONS: SMF treatment enhanced osteoblastic and/or cementoblastic differentiation in osteoblasts, cementoblasts, and PDLCs. These findings provide a molecular basis for the beneficial osteogenic and/or cementogenic effect of SMFs, which could have potential in stimulating bone or cementum formation during bone regeneration and in patients with periodontal disease.
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Humans , Alkaline Phosphatase , Blotting, Western , Bone Regeneration , Calcium , Dental Cementum , Dental Prosthesis , Gene Expression , Glycogen Synthase , Guided Tissue Regeneration, Periodontal , Immunohistochemistry , JNK Mitogen-Activated Protein Kinases , Magnetic Fields , Miners , Osteoblasts , Periodontal Diseases , Periodontal Ligament , Phosphorylation , Polymerase Chain Reaction , Protein Kinases , Regeneration , Relative Biological Effectiveness , Reverse Transcription , RNA, Messenger , Signal Transduction , Wnt ProteinsABSTRACT
Abstract The present review aims to offer an educational approach related to the limitations in the use of the effective dose mgnitude as a tool for the quantification of doses resulting from diagnostic applications of ionizing radiation. We present a critical analysis of the quantities accepted and currently used for dosimetric evaluation in diagnostic imaging procedures, based on studies published in the literature. It is highlighted the use of these quantities to evaluate the risk attributed to the procedure and to calculate the effective dose, as well as to determine its correct use and interpretation.
Resumo Este trabalho de revisão pretende oferecer uma abordagem educacional relacionada às limitações na utilização da grandeza dose efetiva como ferramenta para quantificação de doses decorrentes de aplicações em diagnóstico médico utilizando radiações ionizantes. Os autores apresentam uma análise crítica sobre as grandezas aceitas e utilizadas atualmente para a avaliação dosimétrica em procedimentos de diagnóstico médico por imagem, tendo como base estudos publicados na literatura. Destacam-se as formas de utilização dessas grandezas para a avaliação do risco atribuído ao procedimento e para o cálculo da dose efetiva e sua correta utilização e interpretação.
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Objective To determine the biological effectiveness of 125I radioactive seeds with continuous low dose rate radiation on the human esophageal cancer cell line KYSE150 in vitro and explore the underlying cellular mechanisms.Methods The cells were divided into three cell groups:control group,single dose radiation group (SDR) and 125I radioactive seeds with continuous low dose rate radiation group (125 I-CLDR).The KYSE150 cells were exposed to radiation of X-ray at a high dose rate of 1.052 Gy/min or 125I radioactive seeds at a low dose rate of 2.77 cGy/h.The responses of KYSE150 cells to two modes of irradiation were evaluated by the colony-forming assay,cell apoptosis as well as cell cycle analysis.Furthermore,the expression levels of γ-H2AX and Bax were detected by Western blot.Results KYSE150 cells were more radiosensitive to 125I-CLDR than SDR.The relative biological effectiveness (RBE) for 125I-CLDR related to SDR was 1.56.Compared with SDR,125I-CLDR yielded more proportions of the early and late apoptosis rate (t =4.07,11.08,P ＜0.05) as well as cells at G2/M phase (t =11.25,P ＜0.05).Moreover,γ-H2AX and Bax expression levels in 125I-CLDR significantly increased compared with SDR.Conclusions Compared with the high dose rate X-ray radiation,the continuous low dose rate radiation of 125I radioactive seeds had stronger inhibition effect on KYSE150 esophageal cancer cells by impairing clonogenic capacity,inducing apoptosis and G2/M cell cycle arrest,and increasing radiosensitivity.
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In the previous review, the physical aspect of heavy particles, with a focus on the carbon beam was introduced. Particle beam therapy has many potential advantages for cancer treatment without increasing severe side effects in normal tissue, these kinds of radiation have different biologic characteristics and have advantages over using conventional photon beam radiation during treatment. The relative biological effectiveness (RBE) is used for many biological, clinical endpoints among different radiation types and is the only convenient way to transfer the clinical experience in radiotherapy with photons to another type of radiation therapy. However, the RBE varies dependent on the energy of the beam, the fractionation, cell types, oxygenation status, and the biological endpoint studied. Thus this review describes the concerns about RBE related to particle beam to increase interests of the Korean radiation oncologists' society.
Subject(s)
Carbon , Cell Fractionation , Oxygen , Photons , Population Characteristics , Protons , Relative Biological EffectivenessABSTRACT
Objective To investigate the effect on bioeffects such as sonoporation and cell killing that induced by domestic ultrasound contrast agent(perfluoropropane-albumin microsphere)and diagnostic ultrasound by microbubble concentration.Methods Suspensions of hepatocyte with microbubbules in different concentrations were exposed to diagnostic ultrasound.The study included blank contrast group(no microbubble,no ultrasound),exposed group(no microbubble,exposed to ultrasound)and 6 microbubble groups in different concentration(with different microbubbule/cell ratios for 1,5,10,50,100 and 200,exposed to ultrasound for 10min).The uptake of fluorescein isothiocyanatedextran(FD500)by hepatocyte was observed and the percentages of sonoporation cells were counted,the cell viability was determined by trypan blue stain immediately after exposure,and apoptosis of ceils were detected by flow cytometry,with double staining of fluorescein isothiocyanate(FITC)-labeled Annexin V/propidium iodide(PI).Results Fluorescence stain results:compared with blank contrast group or exposed group,the sonoporatin of groups with microbubble/cell ratio of 5 to 200 increased significantly(P＜0.05).Cell killing effects:compared with the blank contrast group,only the cell death percentages of microbubble groups with microbubble/cell ratio of 50,100 and 200 increased significantly(P＜0.05).Compared with the exposed group,only that of groups with microbubble/cell ratio of 100 and 200 increased significantly(P＜0.05).There was no significant different between blank contrast group and exposed group for all these results.Conclusions Sonoporation and cell killing effect can be induced by diagnostic ultrasound in HL-7702 with domestic ultrasound contrast agent(perfluoropropane-albumin microsphere).For diagnosis,the ratio of microbubbule/cell should better be under 10.While for gene transfection,the ratio should better be 50 and could be 100 if it is necessary.
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The dose response of the number of micronuclei in cytokinesis-blocked (CB) lymphocytes after in vitro irradiation with -rays and neutrons in the 5 dose ranges was studied for a heterogeneous population of 4 donors. One thousand binucleated cells were systematically scored for micronuclei. Measurements performed after irradiation showed a dose-dependent increase in micronuclei(MN) frequency in each of the doctors studied. The dose-response curves were analyzed by a linear-quadratic model, frequencies per 1000 CB cells were (0.31+/-0.049) D+(0.0022+/-0.0002) D2+(13.19+/-1.854) (r2=1.000, X2=0.7074, p=0.95) following irradiation, and (0.99+/-0.528) D+(0.0093+/-0.0047) D2+(13.31+/-7.309) (r2=0.996, X2=7.6834, p=0.11) following neutrons irradiation (D is irradiation dose in cGy). The relative biological effectiveness (RBE) of neutrons compared with -rays was estimated by best fitting linear-quadratic model. In the micronuclei frequency between 0.05 and 0.8 per cell, the RBE of neutrons was 2.37+/-0.17. Since the MN assay is simple and rapid, it may be a good tool for evaluating the y-ray and neutron response.