Energy loss of hydrogen- and helium-ion beams in DNA: calculations based on a realistic energy-loss function of the target

We have calculated the electronic energy loss of proton and α-particle beams in dry DNA using the dielectric formalism. The electronic response of DNA is described by the MELF-GOS model, in which the outer electron excitations of the target are accounted for by a linear combination of Mermin-type energy-loss functions that accurately matches the available experimental data for DNA obtained from optical measurements, whereas the inner-shell electron excitations are modeled by the generalized oscillator strengths of the constituent atoms. Using this procedure we have calculated the stopping power and the energy-loss straggling of DNA for hydrogen- and helium-ion beams at incident energies ranging from 10 keV/nucleon to 10 MeV/nucleon. The mean excitation energy of dry DNA is found to be I = 81.5 eV. Our present results are compared with available calculations for liquid water showing noticeable differences between these important biological materials. We have also evaluated the electron excitation probability of DNA as a function of the transferred energy by the swift projectile as well as the average energy of the target electronic excitations as a function of the projectile energy. Our results show that projectiles with energy ?100 keV/nucleon (i.e., around the stopping-power maximum) are more suitable for producing low-energy secondary electrons in DNA, which could be very effective for the biological damage of malignant cells.     

Microdosimetry of electron microbeams

Track structures of 25, 50 and 80 keV primary electrons, simulated by the detailed-history Monte Carlo method, were analyzed for the frequency distributions of energy deposited in spheres with a diameter of 1 microm, placed in a cylindrically symmetrical array around the projected initial direction of the primary electron. The frequency mean of specific energy, the dose mean of lineal energy, and the parameters of lognormal functions fit to the dose distributions were calculated as a function of beam penetration and radial distance from the projected beam axis. Given these data, the stochastics of dose and radiation quality for micrometer-scale sites targeted by a medium-energy electron microbeam can be predicted as a function of the site's location relative to the beam entry point.     

Comparative microdosimetry of photoelectrons and Compton electrons: an analysis in terms of generalized proximity functions

A current discussion on mammography screening is focused on claims of high relative biological effectiveness (RBE) of mammography X rays compared to conventional 200 kV X rays. An earlier assessment in terms of the electron spectra of these radiations has led to the conclusion that the RBE is bound to be less than 2, regardless of specific model assumptions and the microdosimetric properties of electrons. The present study extends this result in terms of the microdosimetric proximity function, t(x), for electrons, which is essentially the spatial auto-correlation function of energy within particle tracks. If pairs of DNA lesions, e.g. chromosome breaks or deletions, bring about the observed damage, the value t(x) determines for a specified radiation the relative frequency of pairs of lesions a distance x apart. The effectiveness of the radiation is thus proportional to an average of the values of t(x) over the distances, x, for which lesions can combine. The analysis suggests that 15 keV electrons can have a low-dose relative biological effectiveness (RBE(M)) of 1.6 relative to 40 keV electrons if the interaction distances do not exceed about 1 micro m. An extension of the concept, the reduced proximity function, t(delta)(x), permits the inclusion of models with an energy threshold, such as delta = 100 eV, 500 eV or 2 keV, for the formation of each of the DNA lesions. This makes it possible to assess the potential impact of the Auger electrons which accompany most photoelectrons, but only a minority of the Compton electrons. It is found that the Auger electrons could make photoelectrons substantially more effective than Compton electrons at energies below 10 keV but not at energies above 15 keV. The conclusions obtained for the RBE of 15 keV electrons relative to 40 keV electrons will be roughly representative of the RBE of mammography X rays relative to conventional 200 kV X rays.     

Zero-loss energy filtering as improved imaging mode in cryoelectronmicroscopy of frozen-hydrated specimens

One of the remaining problems in attaining higher structural resolution with cryoelectronmicroscopy of frozen-hydrated specimens is the low contrast of micrographs taken close to the electron optical focus. By measuring electron energy loss spectra (EELS) of ice layers we show that a large fraction of incident electrons undergoes an inelastic electron-plasmon scattering process. Thus these electrons do not carry structural information of the protein but increase the background of the electron image and therefore reduce the contrast of the negative. Here we report the improvement in contrast gained by filtering out inelastically scattered electrons using an energy-filtered transmission electron microscope (EFTEM). This gain in contrast permits a dramatic decrease in defocusing values, resulting in improved structural resolution. In addition, the increased signal to noise ratio allows the recording of micrographs at a reduced electron dose. This should result in less damage to vitrified and unstained proteins and other beam-sensitive specimens.     

Monte Carlo simulation of strand-break induction on plasmid DNA in aqueous solution by monoenergetic electrons

The radiation-induced process of strand breaks on pBR322 plasmid DNA in aqueous solution for different energy electrons was studied by Monte Carlo simulation. Assumptions of induction mechanisms of single- and double-strand breaks (SSBs and DSBs) used in the simulation are that SSB is induced by OH or H reaction with DNA and that DSB is induced by two SSBs on the opposite strands within 10 bp. Dose-response relationships of SSBs and DSBs were demonstrated for monoenergetic electrons of 100 eV, 10 keV, 1 keV and 1 MeV, and the yields of SSB and DSB were calculated. The dose-response relationships of SSBs and DSBs can be fitted by linear and linear-quadratic functions, respectively. The ratio of quadratic to linear components of DSB induction changes due to the electron energy. A high contribution of the linear component is observed for 1 keV electrons in the dose range below 160 Gy. The yields of SSBs and DSBs for all examined electron energies lie well within the experimental data when the probability of strand-break induction by OH and H is assumed to be around 0.1-0.2. The yield of SSBs has a minimum at 1 keV, while the yield of DSBs has a maximum at 1 keV in the examined energies. The strand breaks are formed most densely for 1 keV electrons.     

Electron spectra and the RBE of X rays

For an assessment of the possible difference in effectiveness between mammography X rays and conventional X rays, the energy and LET spectra of the released electrons are examined. At photon energies below 20 keV and above 100 keV, the energy of the electrons increases with increasing photon energy, which implies that higher-energy photons produce less densely ionizing radiation and are therefore somewhat less effective per unit dose. However, in the intermediate energy range from 20 keV to 100 keV-the range that is relevant to medical diagnostics-the change from the photoelectric effect to the Compton effect causes a transient decrease of electron energies. The ionization density is therefore similar for 200 kVp X rays and 30 kVp mammography X rays, and the distributions of dose in LET suggest an RBE of 30 kVp mammography X rays compared to 200 kVp X rays of up to 1.3. This is in line with an earlier assessment by Brenner and Amols in terms of microdosimetric data, but it is strongly at variance with a recent claim that X rays for mammography are about four times more effective at small doses than conventional X rays and that they cause a correspondingly greater risk for breast cancer. Since LET need not be the only relevant factor, general response functions are examined here that specify-at low dose-the effect per electron of initial energy E and account, for example, for a particular role of the electron range. It is shown that, with any response per electron track that is a nondecreasing function of its starting energy, the low-dose RBE of the mammography X rays relative to the 200 kVp X rays must be substantially less than 2. The Auger electron that accompanies most photoelectrons, but only a minority of the Compton electrons, may increase the effectiveness of the mammography X rays somewhat, but it cannot explain the reported high values of the RBE.     

Quantitative analysis of knock-on and thermal damage of biological specimens by electron irradiation in transmission electron microscopy

High-energy electrons are able to transfer momentum to nuclei, which results in displacement on to the interstitial lattice sites with a maximum transferred energy of 4 · 10⁴ eV for carbon at 100 keV. Moreover, most of the energy dissipated in energy losses is converted into heat, which results in melting and evaporation.The specimen temperature rise was calculated by the heat conduction theory and confirmed by the specimen drift due to the thermal damage. The damage can be reduced by a small area of illumination, the use of a metal-coated microgrid and small area scanning.A further displacement due to the knock-on collision and the resulting etching rate of biological specimens was measured. The damage is proportional to the current density in c cm^-2 at the specimen. The allowable maximum dose was obtained from the measurement of an etching rate with the weight loss and dry density of the specimens.It was found that the images affected by the electron irradiation, in which -H, C-H, C-N bonds break molecules in proteinaceous biological specimens are removed, and the remaining molecules are changed to stable carbon-rich molecules by deposition, polymerization and contamination. In addition, defect images were observed in high contrast, when compared with unaffected images taken with a small area scanning method.     

Radiobiology of ultrasoft X rays. III. Normal human fibroblasts and the significance of terminal track structure in cell inactivation

Ultrasoft characteristic X rays from carbon (0.28 keV) are severely attenuated as they pass through biological material, causing a nonuniform distribution of dose to cell nuclei. Complications of studying ultrasoft X rays can be minimized in this context by using cells with very thin cytoplasm and nuclei (e.g., less than the attenuation length of the X rays), and which exhibit a more nearly exponential dose response to cell killing, such as normal human fibroblasts compared with V79 cells. Using this cell system, we report the relative biological effectiveness (RBE) of A1-K and C-K X rays to be near unity. Previous studies of cell inactivation by characteristic carbon X rays gave RBEs of 3 to 4, supporting the idea that localized energy depositions from secondary electrons and primary track ends represent the principal mode of biological action for other low-LET radiations. In part, the reported high RBEs result from the use of mean dose to describe energy deposited within the cell nuclei by these poorly penetrating radiations. Implicit in the use of mean dose is that cellular damage varies linearly with dose within a critical target(s), an assumption that is of questionable validity for cells that exhibit pronounced curvilinear dose responses. The simplest interpretation of the present findings is that most energy depositions caused by track-end effects are not necessarily more damaging than the sparsely ionizing component.     

Simulation of electron-beam irradiation of skin tissue model

Monte Carlo simulation of electrons stopping in liquid water was used to model the penetration and quality of electron-beam irradiation incident on the full-thickness EpiDerm? skin model (EpiDermFT? MatTek, Ashland, VA). This 3D tissue model has a fully developed basement membrane separating an epidermal layer of keratinocytes in various stages of differentiation from a dermal layer of fibroblasts embedded in collagen. The simulations were motivated by a desire to selectively expose the epidermal layer to low-linear energy transfer (LET) radiation in the presence of a nonirradiated dermal layer. The variable-energy electron microbeam at the Pacific Northwest National Laboratory (PNNL) was used as a model of device characteristics and irradiation geometry. At the highest beam energy available (90 keV), we estimate that no more than a few percent of the beam energy will be deposited in the dermal layer. Energy deposition spectra were calculated for 10-μm-thick layers near the 10th, 50th and 90th percentiles of penetration by the 90 keV electron beam. Bimodal spectra showed an increasing component of "stoppers" with increasing depth, which increases the probability of large energy deposition events. Nevertheless, screening by tissue above the layer of interest is the main factor determining energy deposited at a given depth.     

Benefits and Limitations of Low-kV Macromolecular Imaging of Frozen-Hydrated Biological Samples

Object contrast is one of the most important parameters of macromolecular imaging. Low-voltage transmission electron microscopy has shown an increased atom contrast for carbon materials, indicating that amplitude contrast contributions increase at a higher rate than phase contrast and inelastic scattering. Here, we studied image contrast using ice-embedded tobacco mosaic virus particles as test samples at 20–80 keV electron energy. The particles showed the expected increase in contrast for lower energies, but at the same time the 2.3-nm-resolution measure decayed more rapidly. We found a pronounced signal loss below 60 keV, and therefore we conclude that increased inelastic scattering counteracts increased amplitude contrast. This model also implies that as long as the amplitude contrast does not increase with resolution, beam damage and multiple scattering will always win over increased contrast at the lowest energies. Therefore, we cannot expect that low-energy imaging of conventionally prepared samples would provide better data than state-of-the-art 200–300 keV imaging.     

A Monte Carlo simulation of Auger cascades

The energy imparted to biological tissue after the decay of incorporated Auger emitters stems from two sources: (a) energy deposition by the Auger and Coster-Kronig electrons and (b) the charge potential which remains on the multiple ionized atom after the end of the cascade. For the numerical assessment of both the kinetic energy of the released electrons and the charge potential, a new and--for purposes of microdosimetry--precise method is presented. Based on relativistic Dirac-Fock calculations and a rigorous bookkeeping, this method provides a perfect energy balance of the considered atomic system when applied to Monte Carlo simulations of Auger cascades. By comparing the results for charge distribution for krypton and iodine with experimental data and the electron spectrum of 125I with theoretical data, it can be shown that the approach followed in this work is reasonable and appropriate for the determination of the energy deposited by incorporated Auger emitters in small volumes of condensed matter. The total energy deposited by 125I in a volume of 20-nm diameter is 2.03 keV which is made up by multiple ionization (1.07 keV) and energy deposition by the emitted Auger electrons (0.96 keV).     

Monte Carlo simulation of the spatial distribution of energy deposition for an electron microbeam

Dosimetry calculations characterizing the spatial variation of the energy deposited by the slowing and stopping of energetic electrons are reported and compared with experimental measurements from an electron microbeam facility. The computations involve event-by-event, detailed-histories Monte Carlo simulations of low-energy electrons interacting in water vapor. Simulations of electron tracks with starting energies from 30 to 80 keV are used to determine energy deposition distributions in thin cylindrical rings as a function of penetration and radial distance from a beam source. Experimental measurements of the spatial distribution of an electron microbeam in air show general agreement with the density-scaled simulation results for water vapor at these energies, yielding increased confidence in the predictions of Monte Carlo track-structure simulations for applications of the microbeam as a single-cell irradiator.     

Effects of radiation damage with 400-kV electrons on frozen, hydrated actin bundles.

Electron images can be used to provide amplitudes and phases for the structural determination of biological specimens. Radiation damage limits the amount of structural information retrievable by computer processing. A 400-kV electron microscope was used to investigate radiation damage effects on frozen, hydrated actin bundles kept at -168 degrees C. The quality of phases within and among images in a damage series was evaluated quantitatively out to 16 A resolution. It was found that the phases of structure factors with good signal-to-noise ratio (IQ less than or equal to 4) can be reliably retrieved from images taken at a cumulative dose of at least 25 electrons/A2.     

Monte Carlo calculations of energy deposition distributions of electrons below 20 keV in protein

The distributions of energy depositions of electrons in semi-infinite bulk protein and the radial dose distributions of point-isotropic mono-energetic electron sources [i.e., the so-called dose point kernel (DPK)] in protein have been systematically calculated in the energy range below 20 keV, based on Monte Carlo methods. The ranges of electrons have been evaluated by extrapolating two calculated distributions, respectively, and the evaluated ranges of electrons are compared with the electron mean path length in protein which has been calculated by using electron inelastic cross sections described in this work in the continuous-slowing-down approximation. It has been found that for a given energy, the electron mean path length is smaller than the electron range evaluated from DPK, but it is large compared to the electron range obtained from the energy deposition distributions of electrons in semi-infinite bulk protein. The energy dependences of the extrapolated electron ranges based on the two investigated distributions are given, respectively, in a power-law form. In addition, the DPK in protein has also been compared with that in liquid water. An evident difference between the two DPKs is observed. The calculations presented in this work may be useful in studies of radiation effects on proteins.     

Monte Carlo simulation of single-cell irradiation by an electron microbeam

A model is presented for irradiation of a cellular monolayer by an electron microbeam. Results are presented for two possible window designs, cells plated on the vacuum-isolation window and cells plated on Mylar above the vacuum-isolation window. Even for the thicker dual-membrane window that facilitates tissue culture and allows the target cell to be centered relative to the electron beam, the majority of the calculated beam spreading was contained in a volume typical of the mammalian HeLa cell line. None of the 10⁴ electrons simulated at 25 keV were scattered into the spatial region occupied by neighbors of the target cell. Dose leakage was largest at 50 keV where the mean energy deposited in all neighbors was 21% of that deposited in the target cell. This ratio was reduced to 5% at 90 keV, the highest beam energy simulated. Lineal energy spectra of energy deposition events scored in the nucleus of the target cell became progressively more like the gamma-ray spectrum as the electron beam energy increased. Hence, our simulations provide strong support for the feasibility of a low-LET, single-cell irradiator. Received: 16 March 2000 / Accepted: 9 May 2000     

Electron stopping power and inelastic mean free path in amino acids and protein over the energy range of 20–20,000 eV

Systematic calculations of stopping power (SPs) and inelastic mean free path (IMFP) values for 20–20,000 eV electrons in a group of 15 amino acids and a simple protein have been performed. The calculations are based on the dielectric response model and take into account the exchange effect between the incident electron and target electrons. The optical energy-loss functions for the 15 investigated amino acids and the protein are evaluated by using an empirical approach, because of the lack of experimental optical data. For all the considered materials, the calculated mean ionization potentials are in good agreement with those given by Bragg’s rule, and the evaluated SP values at 20 keV converge well to the Bethe–Bloch predictions. The data shown represent the first results of SP and IMFP, for these 15 amino acids and the protein in the energy range below 20 keV, and might be useful for studies of various radiation effects in these materials. In addition, the average energy deposited by inelastic scattering of the electrons on this group of 15 amino acids, on the protein, on Formvar and on DNA, respectively, has been estimated for energies below 20 keV. The dependences of the average energy deposition on the electron energy are given. These results are important for any detailed studies of radiation-induced inactivation of proteins and the DNA.     

Calculation of the proximity function of electrons

A new semianalytical method to calculate the proximity function for electrons is proposed. An integral equation for the proximity function that can be solved by using information on the spatial dose distributions is obtained. The proximity function for electrons in the energy range from 10 eV to 10 keV is calculated by solving the equation numerically, using a set of electron collision cross sections for water vapor. The results are in good agreement with those obtained using the Monte Carlo method. The proposed method can be used for electrons of high energies much more efficiently than the Monte Carlo method.     

Considerations of coherent scattering and electron binding in incoherent scattering, in computation of dose deposition in tissue from low-energy photon beams

Two different sets of Monte Carlo computations were carried out for the study of dose penetration of monoenergetic, low-energy (10 to 100 keV) photon beams incident on slabs of tissue. One program took into account coherent scattering and considered electron binding when finding the angle of scattering during incoherent scattering; the other simpler program, customarily used at higher energies, largely ignored these effects. For calculations at the source photon energy of 100 keV, it was found that there was negligible difference in dose distribution in the slab between the more and less complex type of calculations. The same thing was found to be true for the 30 and 10-keV source photon energies only for shallow penetration distances; and at deeper penetrations the simple approach tended to overestimate the dose appreciably. It is concluded that for penetration of low-energy photon beams into tissue, accurate calculational results cannot be assured with the neglect of coherent scattering effects and electron binding considerations in determining the scattering angles except for shallow depths of penetration.     

A high-power vircator operating as an X-ray bremsstrahlung generator

Avircator capable of generating high-power X-ray pulses due to the multiple transitions of electrons through a thin anode foil transparent to X radiation has been created and put into operation for the first time. The vircator is created on the basis of a direct-action electron accelerator supplied from an inductive energy storage operating with a plasma opening switch. Self-consistent two-dimensional simulations of the electron beam dynamics in the vircator chamber are performed, and the spectra of the generated microwave radiation are determined. Self-consistent one-dimensional simulations of the beam dynamics with allowance for electron scattering in the foil were also carried out, and the X-ray bremsstrahlung spectra were measured. Results are presented from the first experiments on the generation of X-ray bremsstrahlung in vircators with thin (10 μm) and thick (100 μm) tantalum anode foils. For a thin foil, the X-ray (E _γ>30 keV) dose is eight times as high as that for a thick foil and the average photon energy is 30 keV (against 80 keV for a thick foil). __________ Translated from Fizika Plazmy, Vol. 30, No. 9, 2004, pp. 828–834. Original Russian Text Copyright ￠ 2004 by Selemir, Dubinov, Ryaslov, Kargin, Efimova, Loyko.     

Comparison between an event-by-event Monte Carlo code,NOREC, and ETRAN for electron scaled point kernels between 20 keV and 1 MeV

An event-by-event Monte Carlo code called NOREC, a substantially improved version of the Oak Ridge electron transport code (OREC), was released in 2003, after a number of modifications to OREC. In spite of some earlier work, the characteristics of the code have not been clearly shown so far, especially for a wide range of electron energies. Therefore, NOREC was used in this study to generate one of the popular dosimetric quantities, the scaled point kernel, for a number of electron energies between 0.02 and 1.0 MeV. Calculated kernels were compared with the most well-known published kernels based on a condensed history Monte Carlo code, ETRAN, to show not only general agreement between the codes for the electron energy range considered but also possible differences between an event-by-event code and a condensed history code. There was general agreement between the kernels within about 5% up to 0.7 r/r ₀ for 100 keV and 1 MeV electrons. Note that r/r ₀ denotes the scaled distance, where r is the radial distance from the source to the dose point and r ₀ is the continuous slowing down approximation (CSDA) range of a mono-energetic electron. For the same range of scaled distances, the discrepancies for 20 and 500 keV electrons were up to 6 and 12%, respectively. Especially, there was more pronounced disagreement for 500 keV electrons than for 20 keV electrons. The degree of disagreement for 500 keV electrons decreased when NOREC results were compared with published EGS4/PRESTA results, producing similar agreement to other electron energies.