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1.
Sci Rep ; 14(1): 8625, 2024 04 14.
Article in English | MEDLINE | ID: mdl-38616193

ABSTRACT

While particle therapy has been used for decades for cancer treatment, there is still a lack of information on the molecular mechanisms of biomolecules radiolysis by accelerated ions. Here, we examine the effects of accelerated protons on highly concentrated native myoglobin, by means of Fourier transform infrared and UV-Visible spectroscopies. Upon irradiation, the secondary structure of the protein is drastically modified, from mostly alpha helices conformation to mostly beta elements at highest fluence. These changes are accompanied by significant production of carbon monoxide, which was shown to come from heme degradation under irradiation. The radiolytic yields of formation of denatured protein, carbon monoxide, and of heme degradation were determined, and found very close to each other: G+denatured Mb ≈ G+CO ≈ G-heme = 1.6 × 10-8 ± 0.1 × 10-8 mol/J = 0.16 ± 0.01 species/100 eV. The denaturation of the protein to a beta structure and the production of carbon monoxide under ion irradiation are phenomena that may play an important role in the biological effects of ionizing radiation.


Subject(s)
Myoglobin , Protons , Carbon Monoxide , Gels , Heme
2.
RSC Adv ; 14(14): 9509-9513, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38516151

ABSTRACT

We elucidate the decomposition mechanism of hydrogen peroxide, which is formed by water radiolysis, by gold nanoparticles (GNPs) under X-ray irradiation. The variations in yields of hydrogen peroxide generated in the presence of GNPs are evaluated using the Ghormley technique. The increase of yields of OH radicals has been quantified using Ampliflu® Red solutions. Almost all hydrogen peroxide generated by irradiation of <25 Gy is decomposed by GNPs, while the yield of OH radicals increases by 1.6 times. The amount of OH radicals thus obtained is almost equivalent to that of the decomposed hydrogen peroxide. The decomposition of hydrogen peroxide is an essential reaction to produce additional OH radicals efficiently in the vicinity of GNPs.

3.
Radiat Res ; 201(4): 287-293, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38407439

ABSTRACT

We report the dose rate dependence of radiation chemical yields (G value) of water radiolysis products under clinical energy protons (230 MeV) to understand mechanisms of the FLASH radiotherapy performed at ultra-high dose rate (>40 Gy/s). The G value of 7-hydoroxy-coumarin-3-carboxylic acid (7OH-C3CA) produced by reactions of coumarin-3-carboxylic acid (C3CA) with OH radicals and oxygen is evaluated by fluorescence method. Also, those of hydrated electrons and hydrogen peroxide are derived by absorption method using Saltzman and Ghomley techniques, respectively. Both G values of 7OH-C3CA and hydrated electrons decrease with increasing dose rate. The relative evolution of 7OH-C3CA is -39 ± 2% between 0.1 and 50 Gy/s. This value is higher than that of hydrated electrons, measured at -21 ± 4%. The G value of hydrogen peroxide in ultra-pure water also decreases with increasing dose rate. In comparison to these findings, we represent the increase of the G value of hydrogen peroxide with increasing dose rate in the mixture solution of MeOH and NaNO3, which act as scavengers of OH radicals and hydrated electrons, respectively, that decompose hydrogen peroxide. This finding indicates that a complex track structure can be expected with increasing dose rate and the reduction of OH radicals by forming hydrogen peroxide would be related to the sparing effect of healthy tissues.


Subject(s)
Hydrogen Peroxide , Protons , Electrons , Water/chemistry
4.
Appl Radiat Isot ; 204: 111125, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38056283

ABSTRACT

This paper reports the relation between latent track structure and the detection threshold of etch pits formation in UPILEX-S® and Kapton. At the similar stopping power value, effective track core radii and G values for heavier ions are lower than those of lighter ions. These results would be due to the difference of the radial dose distribution for low- and high-velocity ions. The G value starts more rapidly rising above 600 and 1000 keV/µm for Kapton and UPILEX-S®, respectively. The detection threshold of UPILEX-S is 4000 keV/µm for Ar ions, at which effective track core radii of all functional groups are larger than 2 nm. Since the length of a molecule unit of UPILEX-S® is about 1.4 nm, at least more than two molecule units have to be damaged for the etch pit formation. A similar discussion is applicable to Kapton, whose detection threshold is significantly lower than UPILEX-S®.

5.
Appl Radiat Isot ; 204: 111100, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38011803

ABSTRACT

This paper reports the variation of track registration sensitivity as a function of the stopping power of heavy ions in UPILEX-S® films, which is known as the most radiation tolerant polyimide (PI). The detection thresholds in the stopping power for etch pit formation are determined as 4,000, 4,100, 4,800, and 5600 keV/µm for 40Ar, 84Kr, 132Xe and 238U ions, respectively. Furthermore, we investigate the latent track structure in two kinds of PI films (UPILEX-S® and Kapton) by means of FT-IR spectroscopy. At the similar stopping power value, the radiation chemical yields (G value) for heavier ions are lower than those of lighter ions. This is due to the difference of the radial dose distribution for low and high velocity ions.

6.
Phys Med Biol ; 69(3)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38157551

ABSTRACT

Objective. Time-dependent yields of chemical products resulting from water radiolysis play a great role in evaluating DNA damage response after exposure to ionizing radiation. Particle and Heavy Ion Transport code System (PHITS) is a general-purpose Monte Carlo simulation code for radiation transport, which simulates atomic interactions originating from discrete energy levels of ionizations and electronic excitations as well as molecular excitations as physical stages. However, no chemical code for simulating water radiolysis products exists in the PHITS package.Approach.Here, we developed a chemical simulation code dedicated to the PHITS code, hereafter calledPHITS-Chemcode, which enables the calculation of theGvalues of water radiolysis species (•OH, eaq-, H2, H2O2etc) by electron beams.Main results.The estimatedGvalues during 1 µs are in agreement with the experimental ones and other simulations. ThisPHITS-Chemcode also simulates the radiolysis in the presence of OH radical scavengers, such as tris(hydroxymethyl)aminomethane and dimethyl sulfoxide. Thank to this feature, the contributions of direct and indirect effects on DNA damage induction under various scavenging capacities can be analyzed.Significance.This chemical code coupled with PHITS could contribute to elucidating the mechanism of radiation effects by connecting physical, physicochemical, and chemical processes.


Subject(s)
Electrons , Water , Water/chemistry , Computer Simulation , Chemical Phenomena , Radiation, Ionizing , Monte Carlo Method
7.
Phys Med Biol ; 69(1)2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38056015

ABSTRACT

Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s-1) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s-1have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed anintegrated microdosimetric-kinetic(IMK)model for UHDR-irradiationenabling the prediction of surviving fraction after UHDR irradiation.Approach.TheIMK model for UHDR-irradiationconsiders the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate.Main results.The estimate by the developed model could successfully reproduce thein vitroexperimental dose-response curve for various cell line types and dose rates.Significance.The developed model would be useful for predicting the biological effects under the UHDR irradiation.


Subject(s)
DNA Damage , DNA Repair , Cell Line , Kinetics , Radiation Tolerance , Radiotherapy Dosage
8.
Phys Chem Chem Phys ; 25(44): 30412-30418, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37916504

ABSTRACT

We investigate the mechanism of damage to the carbonate ester chemical functions in Poly allyl diglycol carbonate (PADC) induced by low-energy electrons (LEEs) of <50 eV, which are major components of the initial secondary products of ionizing radiation. PADC is the world's most widely used polymeric nuclear track detector (PNTD) for swift ion detection. Using diethylene glycol monoethyl ether acetate as a surrogate for PADC, we have measured for irradiation with low-energy electrons (LEEs) of <50 eV, the electron stimulated desorption (ESD) signal of O- from 3-monolayer thick films of DGMEA by time-of-flight mass spectrometry. We find that for electron irradiation at energies >6-9 eV, the instantaneous ESD yield of O- increases with the cumulative number of incident electrons (i.e., fluence), indicating that the additional O- signal derives from an electron-induced DGMEA product. From comparison with ESD measurements from films of acetic acid and acetaldehyde, we identify that the additional desorbed O- signal derives from oxygen atoms originally adjacent to the carbonyl bond in DGMEA. Since LEEs are the predominant secondary particles produced by ionizing radiation, this finding helps to better understand the mechanism of damage to carbonate ester in PADC, which is a key step for latent track formation in PADC.

9.
Cancer Sci ; 114(12): 4548-4557, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37786999

ABSTRACT

Following carbon ion beam irradiation in mammalian cells, such as used in carbon ion radiotherapy (CIRT), it has been suggested that the balance between whether nonhomologous end joining (NHEJ) or homologous recombination (HR) is utilized depends on the DNA double-strand break (DSB) complexity. Here, we quantified DSB distribution and identified the importance of each DSB repair pathway at increasing depths within the carbon ion spread-out Bragg peak (SOBP) beam range. Chinese hamster ovary (CHO) cell lines were irradiated in a single biological system capable of incorporating the full carbon ion SOBP beam range. Cytotoxicity and DSB distribution/repair kinetics were examined at increasing beam depths using cell survival as an endpoint and γ-H2AX as a surrogate marker for DSBs. We observed that proximal SOBP had the highest number of total foci/cell and lowest survival, while distal SOBP had the most dense tracks. Both NHEJ- and HR-deficient CHO cells portrayed an increase in radiosensitivity throughout the full carbon beam range, although NHEJ-deficient cells were the most radiosensitive cell line from beam entrance up to proximal SOBP and demonstrated a dose-dependent decrease in ability to repair DSBs. In contrast, HR-deficient cells had the greatest ratio of survival fraction at entrance depth to the lowest survival fraction within the SOBP and demonstrated a linear energy transfer (LET)-dependent decrease in ability to repair DSBs. Collectively, our results provide insight into treatment planning and potential targets to inhibit, as HR was a more beneficial pathway to inhibit than NHEJ to enhance the cell killing effect of CIRT in targeted tumor cells within the SOBP while maintaining limited unwanted damage to surrounding healthy cells.


Subject(s)
DNA Breaks, Double-Stranded , DNA Repair , Cricetinae , Animals , Humans , Cricetulus , CHO Cells , DNA , Carbon , DNA End-Joining Repair
10.
Phys Med Biol ; 68(15)2023 07 26.
Article in English | MEDLINE | ID: mdl-37429310

ABSTRACT

Objective.FLASH radiation therapy with ultrahigh dose rates (UHDR) has the potential to reduce damage to normal tissue while maintaining anti-tumor efficacy. However, rapid and precise dose distribution measurements remain difficult for FLASH radiation therapy with proton beams. To solve this problem, we performed luminescence imaging of water following irradiation by a UHDR proton beam captured using a charge-coupled device camera.Approach. We used 60 MeV proton beams with dose rates of 0.03-837 Gy s-1from a cyclotron. Therapeutic 139.3 MeV proton beams with dose rates of 0.45-4320 Gy s-1delivered by a synchrotron-based proton therapy system were also tested. The luminescent light intensity induced by the UHDR beams was compared with that produced by conventional beams to compare the dose rate dependency of the light intensity and its profile.Main results. Luminescence images of water were clearly visualized under UHDR conditions, with significantly shorter exposure times than those with conventional beams. The light intensity was linearly proportional to the delivered dose, which is similar to that of conventional beams. No significant dose-rate dependency was observed for 0.03-837 Gy s-1. The light-intensity profiles of the UHDR beams agreed with those of conventional beams. The results did not differ between accelerators (synchrotron or cyclotron) and beam energies.Significance. Luminescence imaging of water is achievable with UHDR proton beams as well as with conventional beams. The proposed method should be suitable for rapid and easy quality assurance investigations for proton FLASH therapy, because it facilitates real-time, filmless measurements of dose distributions, and is useful for rapid feedback.


Subject(s)
Proton Therapy , Radiation Injuries , Humans , Protons , Luminescence , Water , Proton Therapy/methods , Light , Radiotherapy Dosage
11.
Int J Radiat Biol ; 99(9): 1405-1412, 2023.
Article in English | MEDLINE | ID: mdl-36731459

ABSTRACT

PURPOSE: Radiation cancer therapy with ultra-high dose rate (UHDR) exposure, so-called FLASH radiotherapy, appears to reduce normal tissue damage without compromising tumor response to therapy. The aim of this study was to clarify whether a 59.5 MeV proton beam at an UHDR of 48.6 Gy/s could effectively reduce the DNA damage of pBR322 plasmid DNA in solution compared to the conventional dose rate (CONV) of 0.057 Gy/s. MATERIALS AND METHODS: A simple system, consisting of pBR322 plasmid DNA in 1× Tris-EDTA buffer, was initially employed for proton beam exposure. We then used formamidopyrimidine-DNA glycosylase (Fpg) enzymes. which convert oxidative base damages of oxidized purines to DNA strand breaks, to quantify DNA single strand breaks (SSBs) and double strand breaks (DSBs) by agarose gel electrophoresis. RESULTS: Our findings showed that the SSB induction rate (SSB per plasmid DNA/Gy) at UHDR and the induction of Fpg enzyme sensitive sites (ESS) were significantly reduced in UHDR compared to CONV. However, there was no significant difference in DSB induction and non-DSB cluster damages. CONCLUSIONS: UHDR of a 59.5 MeV proton beam could reduce non-clustered, non-DSB damages, such as SSB and sparsely distributed ESS. However, this effect may not be significant in reducing lethal DNA damage that becomes apparent only in acute radiation effects of mammalian cells and in vivo studies.


Subject(s)
DNA , Protons , Animals , Dose-Response Relationship, Radiation , DNA/radiation effects , Plasmids/genetics , DNA Damage , Oxidative Stress , Mammals/genetics
12.
Radiat Res ; 198(3): 255-262, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35738014

ABSTRACT

It has been observed that healthy tissues are spared at ultra-high dose rate (UHDR: >40 Gy/s), so called FLASH effect. To elucidate the mechanism of FLASH effect, we evaluate changes in radiation chemical yield (G value) of 7-hydroxy-coumarin-3-carboxylic acid (7OH-C3CA), which is formed by the reaction of hydroxyl radicals with coumarin-3-carboxylic acid (C3CA), under carbon ions (140 MeV/u) and protons (27.5 and 55 MeV) in a wide-dose-rate range up to 100 Gy/s. The relative G value, which is the G value at each dose rate normalized by that at the conventional dose (CONV: 0.1 Gy/s >), 140 MeV/u carbon-ion beam is almost equivalent to 27.5 and 55 MeV proton beams. This finding implies that UHDR irradiations using carbon-ion beams have a potential to spare healthy tissues. Furthermore, we evaluate the G value of 7OH-C3CA under the de-oxygenated condition to investigate roles of oxygen to the generation of 7OH-C3CA effect. The G value of 7OH-C3CA under the de-oxygenated condition is lower than that under the oxygenated condition. The G value of 7OH-C3CA under the de-oxygenated condition is higher than those under UHDR irradiations. By direct measurements of the oxygen concentration during 55 MeV proton irradiations, the oxygen concentration drops by 0.1%/Gy, which is independent of the dose rate. When the oxygen concentration directly affects to yields of 7OH-C3CA, the rate of decrease in the oxygen concentration may be correlated with that of decrease in the G value of 7OH-C3CA. However, the reduction rate of G value under UHDR is significantly higher than the oxygen consumption. This finding implied that the influence of the reaction between water radiolysis species formed by neighborhood tracks could be strongly related to the mechanisms of UHDR effect.


Subject(s)
Proton Therapy , Protons , Carbon , Coumarins , Ions , Oxygen
13.
Sci Rep ; 12(1): 8957, 2022 05 27.
Article in English | MEDLINE | ID: mdl-35624130

ABSTRACT

The aim of this work is to estimate the biological effect of targeted radionuclide therapy using Cu-64, which is a well-known Auger electron emitter. To do so, we evaluate the absorbed dose of emitted particles from Cu-64 using the Geant4-DNA Monte Carlo simulation toolkit. The contribution of beta particles to the absorbed dose is higher than that of Auger electrons. The simulation result agrees with experimental ones evaluated using coumarin-3-carboxylic acid chemical dosimeter. The simulation result is also in good agreement with previous ones obtained using fluorescent nuclear track detector. From the results of present simulation (i.e., absorbed dose estimation) and previous biological experiments using two cell lines (i.e., evaluation of survival curves), we have estimated the relative biological effectiveness (RBE) of Cu-64 emitted particles on CHO wild-type cells and xrs5 cells. The RBE of xrs5 cells exposed to Cu-64 is almost equivalent to that with gamma rays and protons and C ions. This result indicates that the radiosensitivity of xrs5 cells is independent of LET. In comparison to this, the RBE on CHO wild-type cells exposed to Cu-64 is significantly higher than gamma rays and almost equivalent to that irradiated with C ions with a linear energy transfer of 70 keV/µm.


Subject(s)
Copper Radioisotopes , Radiopharmaceuticals , Animals , CHO Cells , Cricetinae , DNA
14.
J Radiat Res ; 63(2): 255-260, 2022 Mar 17.
Article in English | MEDLINE | ID: mdl-34952540

ABSTRACT

Radiation cancer therapy with ultra-high dose rate exposure, so called FLASH radiotherapy, appears to reduce normal tissue damage without compromising tumor response. The aim of this study was to clarify whether FLASH exposure of proton beam would be effective in reducing the DNA strand break induction. We applied a simple model system, pBR322 plasmid DNA in aqueous 1 × TE solution, where DNA single strand breaks (SSBs) and double strand breaks (DSBs) can be precisely quantified by gel electrophoresis. Plasmid DNA were exposed to 27.5 MeV protons in the conventional dose rate of 0.05 Gy/s (CONV) and ultra-high dose rate of 40 Gy/s (FLASH). With both dose rate, the kinetics of the SSB and DSB induction were proportional to absorbed dose. The SSB induction of FLASH was significantly less than CONV, which were 8.79 ± 0.14 (10-3 SSB per Gy per molecule) and 10.8 ± 0.68 (10-3 SSB per Gy per molecule), respectively. The DSB induction of FLASH was also slightly less than CONV, but difference was not significant. Altogether, 27.5 MeV proton beam at 40 Gy/s reduced SSB and not DSB, thus its effect may not be significant in reducing lethal DNA damage that become apparent in acute radiation effect.


Subject(s)
DNA Damage , Protons , DNA/radiation effects , Dose-Response Relationship, Radiation , Plasmids , Water
15.
Life Sci Space Res (Amst) ; 31: 71-79, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34689952

ABSTRACT

Energetic ion beam experiments with major space radiation elements, 1H, 4He, 16O, 28Si and 56Fe, have been conducted to investigate the radiation shielding properties of composite materials. These materials are expected to be used for parts and fixtures of space vehicles due to both their mechanical strength and their space radiation shielding capabilities. Low Z materials containing hydrogen are effective for shielding protons and heavy ions due to their high stopping power and large fragmentation cross section per unit mass. The stopping power of the composite materials used in this work is intermediate between that of aluminum and polyethylene, which are typical structural and shielding materials used in space. The total charge-changing cross sections per unit mass, σUM, of the composite materials are 1.3-1.8 times larger than that of aluminum. By replacing conventional aluminum used for spacecraft with commercially available composite (carbon fiber / polyether ether ketone), it is expected that the shielding effect is increased by ∼17%. The utilization of composite materials will help mitigate the space radiation hazard on future deep space missions.


Subject(s)
Cosmic Radiation , Heavy Ions , Radiation Protection , Space Flight , Polyethylene , Radiation Dosage , Spacecraft
16.
Sci Rep ; 11(1): 16283, 2021 Aug 11.
Article in English | MEDLINE | ID: mdl-34381072

ABSTRACT

A new diagnosis method for the discriminative detection of laser-accelerated multi-MeV carbon ions from background oxygen ions utilizing solid-state nuclear track detectors (SSNTDs) is proposed. The idea is to combine two kinds of SSNTDs having different track registration sensitivities: Bisphenol A polycarbonate detects carbon and the heavier ions, and polyethylene terephthalate detects oxygen and the heavier ions. The method is calibrated with mono-energetic carbon and oxygen ion beams from the heavy ion accelerator. Based on the calibration data, the method is applied to identify carbon ions accelerated from multilayered graphene targets irradiated by a high-power laser, where the generation of high-energy high-purity carbon ions is expected. It is found that 93 ± 1% of the accelerated heavy ions with energies larger than 14 MeV are carbons. The results thus obtained support that carbon-rich heavy ion acceleration is achieved.

17.
J Nucl Med ; 62(10): 1468-1474, 2021 10.
Article in English | MEDLINE | ID: mdl-33547212

ABSTRACT

A liver metastasis from a primary gastric cancer (LMGC) is relatively common and results in an extremely poor prognosis due to a lack of effective therapeutics. We here demonstrate in a clinically relevant mouse model that an α-particle radioimmunotherapy approach with 211At-labeled trastuzumab has efficacy against LMGCs that are positive for human epidermal growth factor receptor 2 (HER2). Methods:211At was produced in a cyclotron via a 209Bi (α,2n) 211At reaction. 211At-trastuzumab was subsequently generated using a single-step labeling method. NCI-N87 cells (HER2-positive human gastric cancer cells) carrying a luciferase gene were intrasplenically transplanted into severe combined immunodeficiency mice to generate an HER2-positive LMGC model. A biodistribution study was then conducted through the intravenous injection of 211At-trastuzumab (1 MBq) into these LMGC xenograft mice. In parallel with this experimental therapy, phosphate-buffered saline, intact trastuzumab, or 211At-nonspecific human IgG (1 MBq) was injected into control groups. The therapeutic efficacy was evaluated by monitoring tumor changes by chemiluminescence imaging. Body weights, white blood cell counts, and serum markers of tissue damage were monitored at regular intervals. Microdosimetry using a CR-39 plastic detector was also performed. Results: The biodistribution analysis revealed an increased uptake of 211At-trastuzumab in the metastasized tumors that reached approximately 12% of the injected dose per gram of tissue (%ID/g) at 24 h. In contrast, its uptake to the surrounding liver was about 4 %ID/g. The LMGCs in the mouse model reduced dramatically at 1 wk after the single systemic injection of 211At-trastuzumab. No recurrences were observed in 6 of 8 mice treated with this single injection, and their survival time was significantly prolonged compared with the control groups, including the animals treated with 211At-nonspecific antibodies. No severe toxicities or abnormalities in terms of body weight, white blood cell number, liver function, or kidney parameters were observed in the 211At-trastuzumab group. Microdosimetric studies further revealed that 211At-trastuzumab had been delivered at an 11.5-fold higher dose to the LMGC lesions than to the normal liver. Conclusion: α-radioimmunotherapy with 211At-trastuzumab has considerable potential as an effective and safe therapeutic option for LMGC.


Subject(s)
Stomach Neoplasms , Antibodies, Monoclonal, Humanized , Humans , Tissue Distribution , Trastuzumab
18.
Sci Rep ; 11(1): 1524, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33452450

ABSTRACT

We evaluate the track segment yield G' of typical water radiolysis products (eaq-, ·OH and H2O2) under heavy ions (He, C and Fe ions) using a Monte Carlo simulation code in the Geant4-DNA. Furthermore, we reproduce experimental results of ·OH of He and C ions around the Bragg peak energies (< 6 MeV/u). In the relatively high energy region (e.g., > 10 MeV/u), the simulation results using Geant4-DNA have agreed with experimental results. However, the G-values of water radiolysis species have not been properly evaluated around the Bragg peak energies, at which high ionizing density can be expected. Around the Bragg peak energy, dense continuous secondary products are generated, so that it is necessary to simulate the radical-radical reaction more accurately. To do so, we added the role of secondary products formed by irradiation. Consequently, our simulation results are in good agreement with experimental results and previous simulations not only in the high-energy region but also around the Bragg peak. Several future issues are also discussed regarding the roles of fragmentation and multi-ionization to realize more realistic simulations.


Subject(s)
Heavy Ion Radiotherapy/methods , Hydrogen Peroxide/chemistry , Water/chemistry , Computer Simulation , DNA/chemistry , Electrons , Heavy Ions , Linear Energy Transfer/physiology , Models, Chemical , Monte Carlo Method , Physical Phenomena
19.
J Radiat Res ; 62(1): 86-93, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33313873

ABSTRACT

We have been studying the effectiveness of direct action, which induces clustered DNA damage leading to cell killing, relative to indirect action. Here a new criterion Direct Ation-Based Biological Effectiveness (DABBLE) is proposed to understand the contribution of direct action for cell killing induced by C ions. DABBLE is defined as the ratio of direct action to indirect action. To derive this ratio, we describe survival curves of mammalian cells as a function of the number of OH radicals produced 1 ps and 100 ns after irradiation, instead of the absorbed dose. By comparing values on the vertical axis of the survival curves at a certain number of OH radicals produced, we successfully discriminate the contribution of direct action induced by C ions from that of indirect action. DABBLE increases monotonically with increasing linear energy transfer (LET) up to 140 keV/µm and then drops, when the survival curves are described by the number of OH radicals 1 ps after irradiation. The trend of DABBLE is in agreement with that of relative biological effectiveness (RBE) of indirect action. In comparison, the value of DABBLE increases monotonically with LET, when the survival curves are described by the number of OH radicals 100 ns after irradiation. This finding implies that the effectiveness of C ion therapy for cancer depends on the contribution of direct action and we can follow the contribution of direct action over time in the chemical phase.


Subject(s)
Hydroxyl Radical/metabolism , Mammals/metabolism , Radiotherapy , Animals , Carbon , Cell Survival/radiation effects , Linear Energy Transfer , Relative Biological Effectiveness , X-Rays
20.
Life Sci Space Res (Amst) ; 26: 69-76, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32718689

ABSTRACT

Geant4 Monte Carlo simulations were carried out to investigate the possible shielding materials of aluminum, polyethylene, hydrides, complex hydrides and composite materials for radiation protection in spacecraft by considering two physical parameters, stopping power and fragmentation cross section. The dose reduction with shielding materials was investigated for Fe ions with energies of 500 MeV/n, 1 GeV/n and 2 GeV/n which are around the peak of the GCR energy spectrum. Fe ions easily stop in materials such as polyethylene and hydrides as opposed to materials such as aluminum and complex hydrides including high Z metals with contain little or no hydrogen. Attenuation of the primary particles in the shielding and fragmentation into more lightly charged and therefore more penetrating secondary particles are competing factors: attenuation acts to reduce the dose behind shielding while fragmentation increases it. Among hydrogenous materials, 6Li10BH4 was one of the more effective shielding materials as a function of mass providing a 20% greater dose reduction compared to polyethylene. Composite materials such as carbon fiber reinforced plastic and SiC composite plastic offer 1.9 times the dose reduction compared to aluminum as well as high mechanical strength. Composite materials have been found to be promising for spacecraft shielding, where both mass and volume are constrained.


Subject(s)
Cosmic Radiation , Protective Devices/statistics & numerical data , Radiation Protection/methods , Spacecraft , Monte Carlo Method , Radiation Dosage , Radiation Protection/instrumentation
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