Radiation induced chromosome aberrations and the poisson distribution

Summary Data on the distribution of dicentrics and acentrics observed when human lymphocytes are cultured for 48 h after irradiation by X-rays,-rays, and neutrons are presented. Analysis shows that for dicentrics, the observed distribution for X-rays,-rays, and fission neutrons may be described by Poisson statistics but for higher energy neutrons overdispersion is observed. The phenomenon of overdispersion is also observed for acentrics irrespective of the radiation used. The possibility that overdispersion results from the variations of dose in sensitive sites leads to the conclusion that for dicentrics the site size is considerably larger than the 1–2 µm diameter derived by applying the dual action theory to the dose effect relationships. This larger site may well be the cell nucleus.     

Monte Carlo calculation of photo-neutron dose produced by circular cones at 18 MV photon beams

Aim

The aim of this study is to calculate neutron contamination at the presence of circular cones irradiating by 18 MV photons using Monte Carlo code.

Monte Carlo characterizations mapping of the (γ,n) and (n,γ) photonuclear reactions in the high energy X-ray radiation therapy

Aim

The aim of this work was to map the characteristics of (n,γ) and (γ,n) reactions in a high energy photon radiation therapy.

Background

Photoneutrons produced in the high energy X-Ray radiation therapy may damage patients and staff. It is due to high RBE of the produced neutrons according to their energy and isotropic emission. Characterization of the photoneutrons can help us in appropriate shielding.

Materials and methods

This study focused on the photoneutron and capture gamma ray phenomena. Characteristics such as dose value, fluence and spectra of both the neutrons and the by produced prompt gamma ray were described.

Results and discussion

Neutron and prompt gamma spectra in different points showed the neutrons to be thermalized when increasing the distance from the linac. Energy of the neutrons changed from about 0.6 MeV at the isocentre to around 10⁻⁰⁸ MeV at the outer door position. Although the neutrons were found as fast neutrons, their spectra showed they were thermal neutrons at the outer door position. Additionally, it was seen that the energy of the gamma rays is higher than the scattered X-ray energy. The energy of gamma rays was seen to be up to 10 MeV while the linac photons had energy lower than 1 MeV. Neutron source strength obtained in this work was in good agreement with the published data, which may be a confirmation of our simulation accuracy.

Conclusion

The study showed that the Monte Carlo simulation can be applied in the radiotherapy and industrial radiation works as a useful and precise estimator. We also concluded that the dose from the prompt gamma ray at the outer door location is higher than the scattered radiation from the linac and should be considered in the shielding.     

Calibrating and testing tissue equivalent proportional counters with37Ar

A method for testing and calibrating tissue equivalent proportional counters with³⁷Ar is described.³⁷Ar is produced by exposure of argon in its normal isotope composition to thermal neutrons. It is shown that - up to volume ratios of 0.01 of argon to the tissue equivalent gas - there is no appreciable effect of the argon admixture on the function of the proportional counter. Conventional calibration methods with characteristic x-rays or with -particles require modifications of the detectors, and they test only small sub-volumes in the counters. In contrast, argon permits calibrations and tests of the resolution that are representative for the entire counter volume and that do not require changes in detector construction. The method is equally applicable to multi-element proportional counters; it is here exemplified by its application to a long cylindrical counter of simplified design that is part of such a multi-element configuration.     

RBE of quasi-monoenergetic 60 MeV neutron radiation for induction of dicentric chromosomes in human lymphocytes

The production of dicentric chromosomes in human lymphocytes by high-energy neutron radiation was studied using a quasi-monoenergetic 60 MeV neutron beam. The average yield coefficient of the linear dose–response relationship for dicentric chromosomes was measured to be (0.146±0.016) Gy⁻¹. This confirms our earlier observations that above 400 keV, the yield of dicentric chromosomes decreases with increasing neutron energy. Using the linear-quadratic dose–response relationship for dicentric chromosomes established in blood of the same donor for ⁶⁰Co γ-rays as a reference radiation, an average maximum low-dose RBE (RBE_M) of 14±4 for 60 MeV quasi-monoenergetic neutrons with a dose-weighted average energy of 41.0 MeV is obtained. A correction procedure was applied, to account for the low-energy continuum of the quasi-monoenergetic spectral neutron distribution, and the yield coefficient α for 60 MeV neutrons was determined from the measured average yield coefficient . For α, a value of (0.115±0.026) Gy⁻¹ was obtained corresponding to an RBE_M of 11±4. The present experiments extend earlier investigations with monoenergetic neutrons to higher energies.     

Dynamic nuclear polarisation of biological matter

Polarised targets as used in high energy physics experiments may be of considerable interest in biological structure research using polarized neutrons. So far, this promising method has been facing difficulties in getting reasonable polarization of the target nuclei. We report on a polarized frozen spin target which has been prepared from an enzyme dissolved in a mixture of heavy water and deuterated propanediol doped with a completely deuterated paramagnetic radical. Clusters of 700 protons defined by the structure of lysozyme embedded in a fully deuterated matrix were polarized to 75% within an hour by 4 mm microwave irradiation in a magnetic field of 2.5 tesla at a temperature of 0.3 K. The polarisation behaviour of biological targets can be compared to the best frozen spin target materials in high energy physics research.     

Therapeutic potential of atmospheric neutrons

Background

Glioblastoma multiform (GBM) is the most common and most aggressive type of primary brain tumour in humans. It has a very poor prognosis despite multi-modality treatments consisting of open craniotomy with surgical resection, followed by chemotherapy and/or radiotherapy. Recently, a new treatment has been proposed – Boron Neutron Capture Therapy (BNCT) – which exploits the interaction between Boron-10 atoms (introduced by vector molecules) and low energy neutrons produced by giant accelerators or nuclear reactors.

Methods

The objective of the present study is to compute the deposited dose using a natural source of neutrons (atmospheric neutrons). For this purpose, Monte Carlo computer simulations were carried out to estimate the dosimetric effects of a natural source of neutrons in the matter, to establish if atmospheric neutrons interact with vector molecules containing Boron-10.

Results

The doses produced (an average of 1 μGy in a 1 g tumour) are not sufficient for therapeutic treatment of in situ tumours. However, the non-localised yet specific dosimetric properties of 10B vector molecules could prove interesting for the treatment of micro-metastases or as (neo)adjuvant treatment. On a cellular scale, the deposited dose is approximately 0.5 Gy/neutron impact.

Conclusion

It has been shown that BNCT may be used with a natural source of neutrons, and may potentially be useful for the treatment of micro-metastases. The atmospheric neutron flux is much lower than that utilized during standard NBCT. However the purpose of the proposed study is not to replace the ordinary NBCT but to test if naturally occurring atmospheric neutrons, considered to be an ionizing pollution at the Earth''s surface, can be used in the treatment of a disease such as cancer. To finalize this study, it is necessary to quantify the biological effects of the physically deposited dose, taking into account the characteristics of the incident particles (alpha particle and Lithium atom) and radio-induced effects (by-stander and low dose effect). One of the aims of the presented paper is to propose to experimental teams (which would be interested in studying the phenomena) a simple way to calculate the dose deposition (allometric fit of free path, transmission factor of brain).     

Absence of AET protection against fast neutrons: Cellular effects

Summary A series of experiments has been undertaken in order to test the biological properties of neutrons produced in the cyclotron of the Institute Ruder Bokovi (IRB) in Zagreb. Protective effect of AET (2-amino ethylisothiuronium bromid hydrobromid) on survival of L cells irradiated by fast neutrons generated in the IRB cyclotron were studied by employing the single cell clonal growth method. For comparison the protective effect of AET after gamma irradiation has also been studied. The most important findings that have emerged from these experiments can be summerized as follows: (1) Protective effect of AET was present after gamma irradiation only. (2) The degree of protection was dependent on AET concentration in the growth medium. (3) No protective effect was found after neutron irradiation. These findings are in agreement with the generaly less efficient protection of this compounds after high-LET irradiation.     

Energy deposition by proton beams of up to 31 MeV in microscopic volumes

Summary The frequency distributions of energy deposition in microscopic volumes for proton beams of various energies and energy spreads were determined by means of a Rossi type proportional counter. Tissue equivalent spherical volumes of 0.6, 0.72, 0.80, 1.00, 1.25, 1.50, 1.75, 2.00 m diameter were simulated. Frequency distributions of energy deposition per unit pathlength are reported and their behaviour as a function of the simulated pathlength, beam energy and energy spread is discussed. The results indicate that energy deposition distributions in microscopic volumes for protons in the range 8–31 MeV are skewsymmetric distributions with a tail on the high energy side, and that degraded beams behave differently from monoenergetic ones. Dose mean lineal energy values have been quoted for beams used in radiobiological experiments.Work partially supported by Grant n° 7900679.96 of the Finalized Project Tumour Growth Control Consiglio Nazionale delle Ricerche, ItalyBiology Directorate, C.E.C., Brussels, Belgium. Presently c/o CNEN, Casaccia, Italy, under contract n° 175-76-BIO I. Radiation Protection Programme of C.E.C. Publication n° 1629     

Radiotherapy dose enhancement using BNCT in conventional LINACs high-energy treatment: Simulation and experiment

Aim

To employ the thermal neutron background that affects the patient during a traditional high-energy radiotherapy treatment for BNCT (Boron Neutron Capture Therapy) in order to enhance radiotherapy effectiveness.

Background

Conventional high-energy (15–25 MV) linear accelerators (LINACs) for radiotherapy produce fast secondary neutrons in the gantry with a mean energy of about 1 MeV due to (γ, n) reaction. This neutron flux, isotropically distributed, is considered as an unavoidable undesired dose during the treatment. Considering the moderating effect of human body, a thermal neutron fluence is localized in the tumour area: this neutron background could be employed for BNCT by previously administering ¹⁰B-Phenyl-Alanine (¹⁰BPA) to the patient.

Materials and methods

Monte Carlo simulations (MCNP4B-GN code) were performed to estimate the total amount of neutrons outside and inside human body during a traditional X-ray radiotherapy treatment.Moreover, a simplified tissue equivalent anthropomorphic phantom was used together with bubble detectors for thermal and fast neutron to evaluate the moderation effect of human body.

Results

Simulation and experimental results confirm the thermal neutron background during radiotherapy of 1.55E07 cm⁻² Gy⁻¹.The BNCT equivalent dose delivered at 4 cm depth in phantom is 1.5 mGy-eq/Gy, that is about 3 Gy-eq (4% of X-rays dose) for a 70 Gy IMRT treatment.

Conclusions

The thermal neutron component during a traditional high-energy radiotherapy treatment could produce a localized BNCT effect, with a localized therapeutic dose enhancement, corresponding to 4% or more of photon dose, following tumour characteristics. This BNCT additional dose could thus improve radiotherapy, acting as a localized radio-sensitizer.     

Evaluation of dose equivalent using a tissue-equivalent ionization chamber and a Geiger-Müller dosimeter

Summary When detailed neutron energy spectrum data are lacking for a mixed field of neutrons and photons, it is permissible when estimating the dose equivalent to assume that the quality factor for the neutrons is 10. With this assumption, it is shown that the responses of a tissue-equivalent ionization chamber and a Geiger-Müller dosimeter can be used to obtain an acceptable approximation of the dose equivalent in the mixed field without requiring precise knowledge of the relative neutron sensitivity of the Geiger-Müller dosimeter.This investigation was supported by Contract EP-78-S-02-4733 from the Department of Energy to the Radiological Research Laboratory/Department of Radiology and by Grant No. CA13696 to the Cancer Center/Institute of Cancer Research, awarded by National Cancer Institute, DHEW     

On pathlength and energy straggling of megavoltage electrons slowing down

Purposeto elucidate the effects of multiple scattering and energy-loss straggling on electron beams slowing down in materials.MethodsEGSnrc Monte Carlo simulations are done using a purpose-written user-code.ResultsPlots are presented of the primary electron’s energy as a function of pathlength for 20 MeV electrons incident on water and tantalum as are plots of the overall distribution of pathlengths as the 20 MeV electrons slow down under various Monte Carlo scenarios in water and tantalum. The distributions range from 1 % to 135 % of the CSDA range in water and from 1 % to 186 % in tantalum. The effects of energy-loss straggling on energy spectra at depth and electron fluence at depth are also presented.ConclusionsThe role of energy-loss straggling and multiple scattering are shown to play a significant role in the range straggling which determines the dose fall-off region in electron beam dose vs depth curves and a significant role in the energy distributions as a function of depth.     

Endogenous respiration reflects the energy load imposed by transport of nonmetabolizable substrates and by induced de novo protein synthesis in Rhodotorula glutinis

Uptake of the nonmetabolizable sugars 6-deoxy-d-glucose, l-rhamnose and l-xylose, which are taken up by a common carrier, stimulated significantly cell respiration in Rhodotorula glutinis. The extra oxygen consumption for uptake (0.5–0.7 equivalents O₂/mol transported sugar) was proportional to the uptake rate and was independent of the K _tvalue of the transport system. Sugars that become metabolized after induction, d-arabinose and methyl--d-glucoside, caused a higher stimulation, 1.4 and 3.6 equivalents O₂/mol respectively, which was reduced to 0.6 equivalents O₂/mol when de novo protein synthesis was blocked by cycloheximide. The stimulation of respiration thus includes a fraction related purely to the energy demand for uptake and another one related to the induced de novo protein synthesis. The net uptake-induced respiration boost was similar with all sugars under study irrespective of their transport systems. The estimated energy demand was equivalent to about 2 ATP/sugar molecule. For comparison, the amino acid analogue -aminoisobutyric acid (AIB) was also investigated; the overall energy demand for its uptake corresponded to the equivalent of about 4 ATP/molecule.Abbreviation AIB -aminoisobutyric acid     

The Development and a Cytogenetic Study of Monosomics of Gossypium Hirsutum L.

Monosomics of cotton (Gossypium hirsutum L.) were obtained by irradiation of pollen by -rays and by irradiation of seeds by thermal neutrons. Many monosomics were derived directly from irradiation, but a number of monosomics were also recovered in the progeny of plants with translocations and of desynaptic plants. Only 28 primary monosomics showed normal pairing at metaphase-1 of meiosis. The others formec rare trivalents or additional univalents. Partial desynapsis was detected in some monosomics. The pollen fertility levels of monosomics are presented. New morphological characters were detected among the monosome plants of cotton.     

Analytical techniques for boron and boron 10 analysis in a solid experimental tumor EO. 771

Summary If a tumor can be preferentially loaded with a suitable boron-10 compound and irradiated with thermal neutrons, malignant cells can be selectively destroyed via the-particle + Li 7-nucleus from the reaction¹⁰B(n,)⁷Li.Neutron capture therapy with two boron-10 amino acid analogs of low toxicity has been tested in recent years: (a) trimethylamine-carboxyborane, (A3) and (b) amine-carboxyborane, (A7). Now the boron-10 glycineamide analog (A8), amineboryl-carboxamide has been synthesized; it contains 13.81% boron (90% Boron 10+10% Boron 11) and shows a very low toxicity in mice. The effects of this compound were tested on the syngeneic solid adenocarcinoma EO 771 on the right hind leg of male C57 BL/6J mice under standard conditions, by measuring tumor volume growth delay and cell cycle changes using flow cytometry. Boron distribution between tumor and muscle was analyzed by emission spectroscopy with inductively coupled plasma (ICP) following injection of a suspension of peanut oil emulsion. In addition, boron-10 concentration in the tumor were analyzed with prompt-activation analysis and neutron capture radiography (Kodak-Pathé LR 115) at the MRR reactor in Brookhaven after i.p. injection of 0.4 mg/g A8.Application of A8 alone (0.4 mg/g i.p.) or thermal neutron irradiation of the tumor EO. 771 produced a tumor growth delay of 1–2 days for tumor volume doubling. Application of the boron 10 glycine-amide analog A8 i.p. plus 510¹² n/cm² resulted in a growth delay of 3–6 days.In contrastintratumoral application of A8 plus 410¹² n/cm² neutrons gave a growth delay of 7–14 days; the fraction of (G2 + M) cells rose from 35% (neutrons alone) to 52%, as evaluated from flow cytometry.Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday     

A comparison of gamma and neutron irradiation on Raji cells: effects on DNA damage, repair, cell cycle distribution and lethality.

The Comet assay (microgel electrophoresis) was used to study DNA damage in Raji cells, a B-lymphoblastoid cell line, after treatment with different doses of neutrons (0.5 to 16 Gy) or gamma rays (1.4 to 44.8 Gy). A better growth recovery was observed in cells after gamma-ray treatments compared with neutron treatments. The relative biological effectiveness (RBE) of neutron in cell killing was determined to be 2.5. Initially, the number of damaged cells per unit dose was approximately the same after neutron and gamma-ray irradiation. One hour after treatment, however, the number of normal cells per unit dose was much lower for neutrons than for gamma rays, suggesting a more efficient initial repair for gamma rays. Twenty-four hours after treatment, the numbers of damaged cells per unit dose of neutrons or gamma rays were again at comparable level. Cell cycle kinetic studies showed a strong G2/M arrest at equivalent unit dose (neutrons up to 8 Gy; gamma rays up to 5.6 Gy), suggesting a period in cell cycle for DNA repair. However, only cells treated with low doses (up to 2 Gy) seemed to be capable of returning into normal cell cycle within 4 days. For the highest dose of neutrons, decline in the number of normal cells seen at already 3 days after treatment was deeper compared with equivalent unit doses of gamma rays. Our present results support different mechanisms of action by these two irradiations and suggest the generation of locally multiply damaged sites (LMDS) for high linear energy transfer (LET) radiation which are known to be repaired at lower efficiency.     

RBE of nearly monoenergetic neutrons at energies of 36 keV-14.6 MeV for induction of dicentrics in human lymphocytes

We examined the induction of dicentric chromosomes in human lymphocytes irradiated in vitro with nearly monoenergetic neutrons at energies in the range of 36 keV–15.0 MeV. For the assessment of the relative biological effectiveness (RBE) both 220 kV x-rays and ⁶⁰Co -rays were used as reference radiations. To avoid potential confounding factors that would influence the outcome of the experiments, only blood from one individual was used. The neutron RBE culture conditions ensured that the chromosome analysis could be performed exclusively in metaphases of the first cell cycle in vitro. For the reference radiation of 220 kV x-rays, the values of RBE_M were found to increase from 16.6 (E_n=36 keV) to the maximum value of 23.4 (E_n=385 keV). For ⁶⁰Co -rays utilized as the reference radiation, the corresponding RBE_M values were found to be higher by a factor of 4. These results agree well with the previously published large data sets of three laboratories on dose-response relationships for dicentrics or dicentrics plus centric rings. They show a similar dependence of RBE on neutron energy.     

Experimental derivation of relative biological effectiveness of A-bomb neutrons in Hiroshima and Nagasaki and implications for risk assessment

Epidemiological data on the health effects of A-bomb radiation in Hiroshima and Nagasaki provide the framework for setting limits for radiation risk and radiological protection. However, uncertainty remains in the equivalent dose, because it is generally believed that direct derivation of the relative biological effectiveness (RBE) of neutrons from the epidemiological data on the survivors is difficult. To solve this problem, an alternative approach has been taken. The RBE of polyenergetic neutrons was determined for chromosome aberration formation in human lymphocytes irradiated in vitro, compared with published data for tumor induction in experimental animals, and validated using epidemiological data from A-bomb survivors. The RBE of fission neutrons was dependent on dose but was independent of the energy spectrum. The same RBE regimen was observed for lymphocyte chromosome aberrations and tumors in mice and rats. Used as a weighting factor for A-bomb survivors, this RBE system was superior in eliminating the city difference in chromosome aberration frequencies and cancer mortality. The revision of the equivalent dose of A-bomb radiation using DS02 weighted by this RBE system reduces the cancer risk by a factor of 0.7 compared with the current estimates using DS86, with neutrons weighted by a constant RBE of 10.     

Analysis of the Disk-to-Disk Energy Transfer Processes in C-Phycocyanin Complexes by Computer Simulation Technique

Based on the crystal structure and spectral properties of C-phycocyanin (C-PC) from cyanobacteria, models for complexes with 2 and 3 C-PC hexamer disks were built and the energy transfer dynamic properties were studied by the use of stochastic computer simulation approach. In addition, an experimental parameter of 0.056 ps^–1, corresponding to a time constant of 18 ps, derived from the previous time-resolved measurement, was used for simulation of the energy transfer process from the three terminal symmetrically equivalent ₈₄ chromophores of the core-linked disk to an ₈₄ chromophore of the allophycocyanin (APC) core. The simulation showed: (1) The disk-to-disk energy transfer can be as fast as several picoseconds. (2) The energy transfer efficiencies from the first disk to the core would depend on the length of the rod (i.e. the number of disks). Efficiencies of 0.95, 0.87, and 0.75 were found for the rods with 1, 2 and 3 hexamer disks, respectively. (3) The energy transfer along a rod in a native phycobilisome (PBS) is probably very close to the one-way manner. It is the core of PBS that makes the excitation energy be transferred fast in a nearly one-way manner.     

Time-dependent thresholds for torpor initiation in the rufous hummingbird (Selasphorus rufus)

Summary Three models for torpor initiation were tested in rufous hummingbirds (Selasphorus rufus) during moult, when these birds appear to avoid the use of torpor. In model 1, the level of energy reserves at which torpor is initiated (the threshold) remains constant throughout the night. In model 2, the threshold declines throughout the night, at a constant rate equivalent to the rate at which energy reserves are depleted during torpor. In model 3, the threshold declines at a rate equivalent to the rate of energy reserve depletion during torpor for most of the night, but at a higher rate (corresponding to the rate of energy expenditure during normothermia) during the final 2 h of the night, when these birds are usually normothermic. Model 1 predicts the most frequent and longest bouts of torpor, whereas model 3 predicts the fewest and shortest bouts. To determine the thresholds for each of 12 birds, food supply was manipulated to induce entry into torpor at different times on successive nights. Threshold slopes matched the predictions of model 3 most closely. Calculations comparing observed incidence of torpor with the predictions of model 1 show that the actual, time-dependent threshold for torpor initiation resulted in a 72% reduction in the number of torpor bouts compared with the number of torpor bouts that should have been initiated by a constant threshold. The advantage of a time-dependent threshold is that, although torpor is initiated when needed to prevent energy reserves from falling below a critical level, the amount of time spent in torpor can be minimized. This may be especially important to rufous hummingbirds during the spring moult, because lowered metabolic rates during torpor probably result in decreased rates of feather replacement during the moult and may thus have consequences for thermoregulation, territorial defence, and timing of the spring migration.