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1.
The aim of the study was to determine the relative biological effectiveness (RBE) of a 60-MeV proton radiotherapy beam at the Institute of Nuclear Physics, Polish Academy of Sciences (IFJ PAN) in Kraków, the first one to operate in Poland. RBE was assessed at the surviving fractions (SFs) of 0.01, 0.1, and 0.37, for normal human fibroblasts from three cancer patients. The cells were irradiated near the Bragg peak of the pristine beam and at three depths within a 28.4-mm spread-out Bragg peak (SOBP). Reference radiation was provided by 6-MV X-rays. The mean RBE value at SF = 0.01 for fibroblasts irradiated near the Bragg peak of pristine beam ranged between 1.06 and 1.15. The mean RBE values at SF = 0.01 for these cells exposed at depths of 2, 15, and 27 mm of the SOBP ranged between 0.95–1.00, 0.97–1.02, and 1.05–1.11, respectively. A trend was observed for RBE values to increase with survival level and with depth in the SOBP: at SF = 0.37 and at the depth of 27 mm, RBE values attained their maximum (1.19–1.24). The RBE values estimated at SF = 0.01 using normal human fibroblasts for the 60-MeV proton radiotherapy beam at the IFJ PAN in Kraków are close to values of 1.0 and 1.1, used in clinical practice.  相似文献   

2.
PurposeIn-vitro radiobiological studies are essential for modelling the relative biological effectiveness (RBE) in proton therapy. The purpose of this study was to experimentally determine the RBE values in proton beams along the beam path for human prostate carcinoma cells (Du-145). RBE-dose and RBE-LETd (dose-averaged linear energy transfer) dependencies were investigated and three phenomenological RBE models, i.e. McNamara, Rørvik and Wilkens were benchmarked for this cell line.MethodsCells were placed at multiple positions along the beam path, employing an in-house developed solid phantom. The experimental setup reflected the clinical prostate treatment scenario in terms of field size, depth, and required proton energies (127.2–180.1 MeV) and the physical doses from 0.5 to 6 Gy were delivered. The reference irradiation was performed with 200 kV X-ray beams. Respective (α/β) values were determined using the linear quadratic model and LETd was derived from the treatment planning system at the exact location of cells.Results and ConclusionIndependent of the cell survival level, all experimental RBE values were consistently higher in the target than the generic clinical RBE value of 1.1; with the lowest RBE value of 1.28 obtained at the beginning of the SOBP. A systematic RBE decrease with increasing dose was observed for the investigated dose range. The RBE values from all three applied models were considerably smaller than the experimental values. A clear increase of experimental RBE values with LETd parameter suggests that proton LET must be taken into consideration for this low (α/β) tissue.  相似文献   

3.
  1. Since photo-phobic reactions in the blue green alga Phormidium uncinatum seem to be triggered by changes of electron flow rates into or out of an electron pool situated in the electron transport chain between photosystem II and I, the effect of inhibitors affecting the electron transport chain has been studied.
  2. Dose response curves of the phobic reaction have been measured by varying the trap energy in double beam light trap experiments with constant pairs of monochromatic light. From these dose response curves the effects of the inhibitors on both types of phobic reactions, i.e. exit reactions and entrance reactions, have been calculated.
  3. Dibromothymoquinone (DBMIB) inhibits the electron transport between the electron pool and photosystem I by preventing the reoxidation of plastoquinone. The phobic entrance reaction, which results in an emptying of the light trap, is triggered by changes in the electron flow out of the pool; thus it is more effected by DBMIB than the exit reaction, which is mediated by the electron transport into the pool.
  4. The phobic exit reaction, which results in accumulations in the light trap, is triggered by changes in the electron flow into the electron pool via photosystem II. 3-[3,4-dichlorophenyl]-1,1-dimethylurea (DCMU) inhibits the electron transport near photosystem II; thus it affects the exit reaction more than the entrance reaction.
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4.
Summary The macroscopic reaction of the mouse skin was used to derive RBE values for negative-Mesons. Hind limbs of mice were irradiated with pions or X-rays. The pions were produced by the 590 MeV accelerator of the Schweizerisches Institut für Nuklearforschung (SIN). Early skin reaction was assessed over a period of 6–30 days after irradiation with single doses (20–45 Gy). The radiation damage was scored using an arbitrary scale of effect. The time pattern of development of the skin reaction and the subsequent healing after exposure both to pions and X-rays were similar, indicating that depletion and repopulation of the basal cells of the skin were comparable, both after pions and X-rays. RBE values as a function of pion doses at the peak (dose maximum), plateau and at the postpeak (12 mm downstream of the dose maximum) were computed with nonparametric statistical methods. The RBE at the peak and at the plateau relative to X-rays of the same dose rate was 1.15–1.25 and 0.85, respectively. The RBE of peak pions manifested a marked dependence on dose, when plateau pions were chosen as reference radiation. In this experiment there was no significant difference in RBE between peak and postpeak. The importance of some experimental condition (dose rate, irradiation volume) is discussed.Supported by the Swiss National Science Foundation (grant no. 3.682-0.75)  相似文献   

5.
The relative biological effectiveness (RBE) of 10B-neutron capture therapy (BNCT) on skin was analyzed using hamsters. The Kyoto University Research Reactor, which has a very low contamination of gamma rays and fast neutrons, was used as a thermal neutron source. Boron-10-para-boronophenylalanine hydrochloride ([10B]BPA.HCl) was administered to the hamsters. The evolution and time course of early skin reactions were assessed. These reactions were compared with those produced by electron beams. The maximum safe skin doses (no more than moist desquamation) of BNCT and electron beams were established to be 11 and 21 Gy, respectively. The RBE at this single dose with BNCT was found to be 1.94, assuming that the RBE of the gamma rays was 1.0 and each component of BNCT (mixed radiations) was simply additive.  相似文献   

6.
Preclinical studies represent an important step towards a deep understanding of the biological response to ionizing radiations. The effectiveness of proton therapy is higher than photons and, for clinical purposes, a fixed value of 1.1 is used for the relative biological effectiveness (RBE) of protons considered 1.1. Recent in vitro studies have reported that the RBE along the spread-out Bragg peak (SOBP) is not constant and, in particular, the RBE value increases on the distal part of SOBP. The present work has been carried-out in the perspective of a preclinical hadrontherapy facility at LNS-INFN and was focused on the experimental preparation of an in vivo study concerning the RBE variation along the SOBP. The main purpose of this work was to determine, using GEANT4-based Monte Carlo simulations, the best configuration for small animal treatments. The developed GEANT4 application simulates the proton-therapy beam line of LNS-INFN (CATANA facility) and allows to import the DICOM-CT images as targets. The RBE will be evaluated using a deterministic radiation damage like myelopathy as end-point. In fact, the dose at which the 50% of animals will show the myelopathy is supposed to be LET-dependent. In this work, we studied different treatment configurations in order to choose the best two that maximize the LET difference reducing as much as possible the dose released to healthy tissue. The results will be useful to plan hadrontherapy treatments for preclinical in vivo studies and, in particular, for the future in vivo RBE studies.  相似文献   

7.
The effect of low doses of 240 kVp X rays or of 3 MeV neutrons has been investigated using skin reactions on mouse feet as the biological system. Eight or nine repeated small doses of radiation were used, followed by graded "top-up" doses to bring the reactions into a detectable range. By comparing dose-response curves, the RBE has been determined for neutron doses per fraction ranging from 0.25-1.0 Gy. The data are consistent with a limiting RBE of between 7 and 10 at very low doses. A review of other published RBE values for low doses per fraction shows a wide range of RBEs . Very few studies show a plateau value for the RBE. These findings are more consistent with dose-response data that fit a linear-quadratic model than with a multitarget single-hit model.  相似文献   

8.
To investigate the potential efficacy of fission neutrons from a fast-neutron reactor for the treatment of radioresistant tumors, the relative biological effectiveness (RBE) and tolerance dose of fission neutrons in canine skin were determined. The forelimbs of 34 healthy mongrel dogs received a single dose of fission neutrons (5.6, 6.8, 8.2, 9.6 or 11 Gy) or 137Cs gamma rays (10, 15, 20, 25 or 30 Gy). Based on observations of radiodermatitis for each radiation, the single-fraction RBE of fission neutrons in the sixth month was calculated as approximately 3. The tolerance doses of fission neutrons and gamma rays, defined as the highest doses giving no moist desquamation on the irradiated skin in the recovery phase, were estimated as 7.6 Gy and 20 Gy, respectively. The tolerance dose of 7.6 Gy of fission neutrons included 5.0 Gy of fast neutrons possessing high anti-tumor effects and 1.4 x 10(12) n/cm2 of thermal neutrons, which could be applicable to neutron capture therapy (NCT). The combination of fast-neutron therapy and NCT using a fast-neutron reactor might be useful for the treatment of radioresistant tumors.  相似文献   

9.
A study was made of the regularities of formation of lenticular opacity in mice exposed to 9 GeV protons and 60Co-gamma-rays. The RBE coefficients, calculated by the nonparametric method, were found to depend upon dose and time after irradiation. It was shown that after small radiation doses (0.25 to 0.50 Gy) the RBE coefficients increased from 1 to 8 with increasing period of observation. With higher doses (up to 5.0 Gy) the RBE coefficient increase in time was less pronounced.  相似文献   

10.
Most information on the dose–response of radiation-induced cancer is derived from data on the A-bomb survivors who were exposed to γ-rays and neutrons. Since, for radiation protection purposes, the dose span of main interest is between 0 and 1 Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses above 1 Gy are becoming more important for radiotherapy patients and for long-term manned missions in space research. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation-induced solid cancer. The analysis of the A-bomb survivor’s data was extended by including two extra high-dose categories (4–6 Sv and 6–13 Sv) and by an attempted combination with cancer data on patients receiving radiotherapy for Hodgkin’s disease. In addition, since there are some recent indications for a high neutron dose contribution, the data were fitted separately for three different values for the relative biological effectiveness (RBE) of the neutrons (10, 35 and 100) and a variable RBE as a function of dose. The data were fitted using a linear, a linear-exponential and a plateau-dose–response relationship. Best agreement was found for the plateau model with a dose-varying RBE. It can be concluded that for doses above 1 Gy there is a tendency for a nonlinear dose–response curve. In addition, there is evidence of a neutron RBE greater than 10 for the A-bomb survivor data. Many problems and uncertainties are involved in combing these two datasets. However, since very little is currently known about the shape of dose–response relationships for radiation-induced cancer in the radiotherapy dose range, this approach could be regarded as a first attempt to acquire more information on this area. The work presented here also provides the first direct evidence that the bending over of the solid cancer excess risk dose response curve for the A-bomb survivors, generally observed above 2 Gy, is due to cell killing effects.  相似文献   

11.
A further study on the response of the mouse kidney to d(4)-Be neutrons (EN = 2.3 MeV) is described. The results confirm and augment the work published previously by Stewart et al. [Br. J. Radiol. 57, 1009-1021 (1984)]; the present paper includes the data from a "top-up" design of experiment which extends the measurements of neutron RBE (relative to 240 kVp X rays) down to X-ray doses of 0.75 Gy per fraction. The mean RBE for these neutrons increases from 5.8 to 7.3 as X-ray dose per fraction decreases from 3.0 to 1.5 Gy in the kidney. This agrees with the predictions from the linear quadratic (LQ) model, based on the renal response to X-ray doses above 4 Gy per fraction. The mean RBE estimate from a single dose group at 0.75 Gy per fraction of X rays is, however, 3.9. This is below the LQ prediction and may indicate increasing X-ray sensitivity at low doses. Data from this study and from those published previously have been used to determine more accurately the shape of the underlying response to d(4)-Be neutrons; an alpha/beta ratio of 20.5 +/- 3.7 Gy was found. The best value of alpha/beta for X rays determined from these experiments was 3.04 +/- 0.35 Gy, in agreement with previous values.  相似文献   

12.

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LETd distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LETd, where higher LETd leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE10). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

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13.
In vitro studies of the relative biological effectiveness (RBE) of 50-MV X rays have shown an RBE of 1.1 relative to 4-MV X rays. This will be important in clinical radiotherapy. The aim of this study was to verify these results and to investigate whether photonuclear processes might cause the difference in RBE. To do so, 50- and 20-MV X rays and 50-MeV electrons were investigated with respect to RBE. Chinese hamster V79 cells were irradiated in a specially designed system which allows for a high reproducibility of geometry and dosimetry. Fractionation experiments were also carried out to establish the RBE at the clinically relevant dose level, 2 Gy. Fricke dosimetry was used, and the results were confirmed with ionization chamber measurements. The RBE for 50-MV X rays was estimated to be 1.14 at a surviving fraction of 0.1 and 1.12 at a surviving fraction of 0.01. The RBEs for the other qualities were equal to one. The RBE calculated for the 2 Gy/fraction experiments was 1.17.  相似文献   

14.
Dose-response curves for micronucleus (MN) formation were measured in Chinese hamster V79 and xrs6 (Ku80(-)) cells and in human mammary epithelial MCF10A cells in the dose range of 0.05-1 Gy. The Chinese hamster cells were exposed to 1 GeV/nucleon iron ions, 600 MeV/nucleon iron ions, and 300 MeV/nucleon iron ions (LETs of 151, 176 and 235 keV/microm, respectively) as well as with 320 kVp X rays as reference. Second-order polynomials were fitted to the induction curves, and the initial slopes (the alpha values) were used to calculate RBE. For the repair-proficient V79 cells, the RBE at these low doses increased with LET. The values obtained were 3.1 +/- 0.8 (LET = 151 keV/microm), 4.3 +/- 0.5 (LET = 176 keV/microm), and 5.7 +/- 0.6 (LET = 235 keV/microm), while the RBE was close to 1 for the repair-deficient xrs6 cells regardless of LET. For the MCF10A cells, the RBE was determined for 1 GeV/nucleon iron ions and was found to be 5.5 +/- 0.9, slightly higher than for V79 cells. To test the effect of shielding, the 1 GeV/nucleon iron-ion beam was intercepted by various thicknesses of high-density polyethylene plastic absorbers, which resulted in energy loss and fragmentation. It was found that the MN yield for V79 cells placed behind the absorbers decreased in proportion to the decrease in dose both before and after the iron-ion Bragg peak, indicating that RBE did not change significantly due to shielding except in the Bragg peak region. At the Bragg peak itself with an entrance dose of 0.5 Gy, where the LET is very high from stopping low-energy iron ions, the effectiveness for MN formation per unit dose was decreased compared to non-Bragg peak areas.  相似文献   

15.
While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.  相似文献   

16.
The aim of this study was to investigate the validity of the ICRP procedure of using average tissue/organ dose in estimating carcinogenic risk. It has been suggested that highly non-uniform exposure ('hot spots') is much more carcinogenic than an equivalent dose delivered uniformly. In a series of experiments, mice were irradiated with X-rays either uniformly to the thorax or non-uniformly with 72 1-mm microbeams which irradiated approximately 20 per cent of the total lung volume. Two experiments involving uniform irradiation showed a peaked tumour incidence curve with a maximum at 5 Gy. The first 'microbeam' study also produced a pronounced peak in the dose response with a maximum tumour incidence at 1 Gy average lung dose or 5 Gy to the irradiated lung tissue. This implied the use of average tissue dose might underestimate the carcinogenic hazard of non-uniform exposure. Later, more extensive, microbeam experiments failed to replicate this finding. The results were nearly similar to those for uniform irradiation, with a slight increase in tumour incidence from 2.5-5.0 Gy average lung dose. These results imply that for these irradiation conditions the ICRP dose averaging procedure remains valid.  相似文献   

17.
Snigireva  G. P.  Khaimovich  T. I.  Nagiba  V. I. 《Biophysics》2011,56(2):364-370
The goal of this work was to determine the relative biological effectiveness (RBE) of tritium β-radiation according to the chromosome aberration frequency in the peripheral blood lymphocytes after in vitro and in vivo radiation exposures. The experimental RBE assessment of tritium β-radiation relative to 60Co γ-radiation according to unstable chromosome aberration frequency in the peripheral blood lymphocytes under particular conditions is described. It has been demonstrated that tritium β-radiation is, in general, more effective in the dose range of up to 1 Gy, which is most pronounced at low doses. The RBE value of tritium β-radiation at minimum doses reached 2.2 and decreased at higher doses (1 Gy) to 1.25. The data on comparative analysis of the frequency of stable chromosome aberrations in the blood lymphocytes of professional nuclear workers (Sarov, Russia) after long-term chronic exposure to tritium β-radiation, as compared with γ-irradiation, are reported for the first time. The higher biological effectiveness of tritium β-radiation was demonstrated and was estimated as 2.5.  相似文献   

18.
The RBE for neutrons was assessed in a head-to-head experiment in which cultures of lymphocytes from the same male donor were irradiated simultaneously with 144 keV neutrons and with 60Co gamma rays as the reference radiation and evaluated using matched time, culture conditions, and the end point of chromosomal aberrations to avoid potential confounding factors that would influence the outcome of the experiment. In addition, the irradiation time was held constant at 2 h for the high-dose groups for both radiation types, which resulted in rather low dose rates. For the induction of dicentric chromosomes, the exposure to the 144 keV neutrons was found to be almost equally as effective (yield coefficient alpha(dic) = 0.786 +/- 0.066 dicentrics per cell per gray) as that found previously for irradiation with monoenergetic neutrons at 565 keV (alpha(dic) = 0.813 +/- 0.052 dicentrics per cell per gray) under comparable exposure and culture conditions (Radiat. Res. 154, 307-312, 2000). However, the values of the maximum low-dose RBE (RBE(m)) relative to 60Co gamma rays that were determined in the present and previous studies show an insignificant but conspicuous difference: 57.0 +/- 18.8 and 76.0 +/- 29.5, respectively. This difference is mainly due to the difference in the alpha(dic) value of the 60Co gamma rays, the reference radiation, which was 0.0138 +/- 0.0044 Gy(-1) in the present study and 0.0107 +/- 0.0041 Gy(-1) in the previous study. In the present experiment, irradiations with 144 keV neutrons and 60Co gamma rays were both performed at 21 degrees C, while in the earlier experiment irradiations with 565 keV neutrons were performed at 21 degrees C and the corresponding reference irradiation with gamma rays was performed at 37 degrees C. However, the temperature difference between 21 degrees C and 37 degrees C has a minor influence on the yield of chromosomal alterations and hence RBE values. The large cubic PMMA phantom that was used for the gamma irradiations in the present study results in a larger dose contribution from Compton-scattered photons compared to the mini-phantom used in the earlier experiments. The contribution of these scattered photons may explain the large value of alpha(dic) for gamma irradiation in the present study. These results indicate that the yield coefficient alpha(dic) for 144 keV neutrons is similar to the one for 565 keV neutrons, and that modification of the alpha(dic) value of the low-LET reference radiation, due to changes in the experimental conditions, can influence the RBE(m). Consequently, alpha(dic) values cannot be shared between cytogenetic laboratories for the purpose of assessment of RBM(m) without verification of the comparability of the experimental conditions.  相似文献   

19.
In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses.  相似文献   

20.
Relative biological effectiveness (RBE) of gamma-neutron radiation with neutron energy of 0.9 MeV was estimated with a reference to rat death. It was shown that RBE of gamma-neutron radiation (the share of neutrons was 67% as related to dose) at LD33/30 and LD100/30 was 2, and RBE of 0.9 MeV neutrons, in experiments with mixed radiation, was 3.1 and 2.86 at LD33/30 and LD100/30, respectively. The value of a maximum dose at which death was not registered during 30 days, was 1 Gy with gamma-neutron radiation and 4 Gy with X-radiation.  相似文献   

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