The production of OH radicals in the radiolysis of water with 4He ions

Formic acid solutions of 1, 10, 100, and 1000 mM have been irradiated with 4He ions of 5 to 25 MeV, and the production of OH radicals has been determined by measuring the yield of CO2. The differential OH radical yields were obtained from the observed energy dependencies; with 25 MeV 4He ions they range from 1.91 to 3.48 molecules/100 eV for formic acid concentrations of 1 to 1000 mM, respectively. The OH radical yields decrease with decreasing particle energy, and at the maximum LET (230 eV/nm) they range from 0.30 at 1 mM to 0.82 molecules/100 eV at 1000 mM. These values are only 15 to 20% of that found with fast electrons. The OH radical yields are relatively more dependent on formic acid concentration at higher 4He ion energies. The average time dependencies of the OH radical from 7.7 ns to 7.7 microseconds were estimated from the formic acid concentration dependencies at various 4He energies. In terms of absolute yields, there is a considerable variation in the yields of OH radicals with time at the highest energies, but at the maximum LET the OH radical yields are nearly invariant with time after about 10 ns.     

Characterization of hydroxyl radical-induced damage after sparsely and densely ionizing irradiation

The extent of hydroxyl radical mediated cell inactivation was measured for a variety of particle beams ranging from 8.5 Me V/u neon ions to 570 Me V/u argon ions. In general, the fraction of the total radiosensitivity caused by OH decreases from close to 60 per cent at low ionization density or low linear energy transfer (low LET) to close to 25 per cent at high LET for aerobically irradiated mammalian cells. The extent of OH induced cell lethality can be explained in terms of LET infinity only for low energy or low atomic number particles where fragmentations and complicated track structures do not contaminate the characteristic particle LET. For example, at a calculated LET infinity of 100 ke V/micron, the OH mediated fraction of the total radiation damage is about 25 per cent for low energy carbon but close to 40 per cent for high energy carbon ions. For low energy charged nuclei of approximately the same energy, as the 5.4-13.4 MeV/u He, Li, C and Ne ions in this report, there is a predictable diminution of the OH mediated effect with increasing LET infinity; however, the biological effect cannot be predicted accurately from calculated LET infinity values for high energy particle irradiation, nor indeed from a variety of low energy charged particles of quite different energies (incident velocities). This illustrates the unsuitability of using LET as a unifying parameter, except under specific circumstances. As more is learned about the energy deposition for energized charged particles in terms of track structure (core and penumbra), it may be possible to characterize the radiobiological data with a better physical parameter than LET infinity.     

Spectrum of complex DNA damages depends on the incident radiation

Ionizing radiation induces bistranded clustered damages--two or more abasic sites, oxidized bases and strand breaks on opposite DNA strands within a few helical turns. Since clusters are refractory to repair and are potential sources of double-strand breaks (DSBs), they are potentially lethal and mutagenic. Although induction of single-strand breaks (SSBs) and isolated lesions has been studied extensively, little is known about the factors affecting induction of clusters other than DSBs. To determine whether the type of incident radiation could affect the yields or spectra of specific clusters, we irradiated genomic T7 DNA, a simple 40-kbp linear, blunt-ended molecule, with ion beams [iron (970 MeV/nucleon), carbon (293 MeV/nucleon), titanium (980 MeV/nucleon), silicon (586 MeV/nucleon), protons (1 GeV/nucleon)] or 100 kVp X rays and then quantified DSBs, Fpg-oxypurine clusters and Nfo-abasic clusters using gel electrophoresis, electronic imaging and number average length analysis. The yields (damages/Mbp Gy(-1)) of all damages decreased with increasing linear energy transfer (LET) of the radiation. The relative frequencies of DSBs compared to abasic and oxybase clusters were higher for the charged particles-including the high-energy, low-LET protons-than for the ionizing photons.     

Track structure in DNA irradiated with heavy ions

The spatial properties of trapped radicals produced in heavy-ion-irradiated solid DNA at 77 K have been probed using pulsed electron paramagnetic double resonance (PELDOR or DEER) techniques. Salmon testes DNA hydrated to 12 water molecules per nucleotide was irradiated with 40Ar ions of energy 100 MeV/nucleon and LET ranging from 300 to 400 keV/microm. Irradiated samples were maintained at cryogenic temperature at all times. PELDOR measurements were made using a refocused echo detection sequence that allows dipolar interaction between trapped radicals to be observed. The EPR spectrum is attributed to electron loss/gain DNA base radicals and neutral carbon-centered radicals that likely arise from sugar damage. We find a radical concentration of 13.5 x 10(18) cm(-3) in the tracks and a track radius of 6.79 nm. The cross section of these tracks is 144 nm2, yielding a lineal radical density of 2.6 radicals/nm. Based on the yields determined previously for particles having calculated LET values of 300-400 keV/microm and our measured lineal density, we obtain an LET of 270 keV/microm, which is in good agreement with the calculated range of values. These measurements of radical density and spatial extent provide the first direct experimental determination of track characteristics in irradiated DNA.     

Contribution of indirect action to radiation-induced mammalian cell inactivation: dependence on photon energy and heavy-ion LET

The contribution of indirect action mediated by OH radicals to cell inactivation by ionizing radiations was evaluated for photons over the energy range from 12.4 keV to 1.25 MeV and for heavy ions over the linear energy transfer (LET) range from 20 keV/microm to 440 keV/microm by applying competition kinetics analysis using the OH radical scavenger DMSO. The maximum level of protection provided by DMSO (the protectable fraction) decreased with decreasing photon energy down to 63% at 12.4 keV. For heavy ions, a protectable fraction of 65% was found for an LET of around 200 keV/microm; above that LET, the value stayed the same. The reaction rate of OH radicals with intracellular molecules responsible for cell inactivation was nearly constant for photon inactivation, while for the heavy ions, the rate increased with increasing LET, suggesting a reaction with the densely produced OH radicals by high-LET ions. Using the protectable fraction, the cell killing was separated into two components, one due to indirect action and the other due to direct action. The inactivation efficiency for indirect action was greater than that for direct action over the photon energy range and the ion LET range tested. A significant contribution of direct action was also found for the increased RBE in the low photon energy region.     

Benchmark studies of the effectiveness of structural and internal materials as radiation shielding for the international space station

Accelerator-based measurements and model calculations have been used to study the heavy-ion radiation transport properties of materials in use on the International Space Station (ISS). Samples of the ISS aluminum outer hull were augmented with various configurations of internal wall material and polyethylene. The materials were bombarded with high-energy iron ions characteristic of a significant part of the galactic cosmic-ray (GCR) heavy-ion spectrum. Transmitted primary ions and charged fragments produced in nuclear collisions in the materials were measured near the beam axis, and a model was used to extrapolate from the data to lower beam energies and to a lighter ion. For the materials and ions studied, at incident particle energies from 1037 MeV/nucleon down to at least 600 MeV/nucleon, nuclear fragmentation reduces the average dose and dose equivalent per incident ion. At energies below 400 MeV/nucleon, the calculation predicts that as material is added, increased ionization energy loss produces increases in some dosimetric quantities. These limited results suggest that the addition of modest amounts of polyethylene or similar material to the interior of the ISS will reduce the dose to ISS crews from space radiation; however, the radiation transport properties of ISS materials should be evaluated with a realistic space radiation field.     

Stochastic radial dose distributions and track structure theory

Measured single-event distributions of the specific energy deposited in cylindrical volumes with simulated diameters down to 150 nm for (4)He and (12)C ions with energies of 25 MeV/nucleon and (16)O ions with 21 MeV/nucleon and radial distances up to 12 microm are presented. The mean specific energy per ion , the mean specific energy per target hit z(1)(r), and the relative frequency of target hits nu(r) as a function of radial distance are evaluated and compared with the corresponding quantities of the track structure model of Kiefer and Straaten (Phys. Med. Biol. 31, 1201-1209, 1986). Though there are some discrepancies in the absolute values, the radial dependence of , z(1)(r) and v(r) for (12)C and (16)O ions is reproduced satisfactorily. The model fails to describe the data for (4)He ions. A more detailed comparison of the radial shape of the mean specific energies calculated from the experimental data from the present work and data from the literature reveals a significant projectile charge dependence which is not included in track structure models.     

OH radicals and oxidizing products in the gamma radiolysis of water

The production of OH radicals in the gamma radiolysis of water has been examined with radical scavenger techniques employing formic acid. OH radical yields were found to vary from 2.4 radicals/100 eV at the low scavenger concentration limit to 4.2 at a formic acid concentration of 3 M. An inverse Laplace transform technique was applied to the scavenger concentration dependence to obtain the temporal dependence of OH radicals in pure water. It was found that the relative decrease in OH radical yields from 200 ps to 3 ns was virtually the same for the transform of the scavenger data and the directly measured time-resolved results. The absolute yields for the time-resolved experiments are about 10% higher than expected from the present results with scavengers. The agreement can be considered to be good, and reasons for the observed difference are given. Approximately 40% of the OH radicals produced lead to the formation of hydrogen peroxide, which is the only other major oxidizing species in the gamma radiolysis of water. The net water decomposition for gamma rays was found to vary from an initial value of 5.6 +/- 0.3 molecules/100 eV to 3.8 +/- 0.2 molecules/100 eV at 1 micros.     

The response of tissue-equivalent proportional counters to heavy ions

The paper presents a theoretical model for the response of a tissue-equivalent proportional counter (TEPC) irradiated with charged particles. Heavy ions and iron ions in particular constitute a significant part of radiation in space. TEPCs are used for all space shuttle and International Space Station (ISS) missions to estimate the dose and radiation quality (in terms of lineal energy) inside spacecraft. The response of the tissue-equivalent proportional counters shows distortions at the wall/cavity interface. In this paper, we present microdosimetric investigation using Monte Carlo track structure calculations to simulate the response of a TEPC to charged particles of various LET (1 MeV protons, 2.4 MeV alpha particles, 46 MeV/nucleon 20Ne, 55 MeV/nucleon 20Ne, 45 MeV/nucleon 40Ar, and 1.05 GeV/nucleon 56Fe). Data are presented for energy lost and energy absorbed in the counter cavity and wall. The model calculations are in good agreement with the results of Rademacher et al. (Radiat. Res. 149, 387-389, 1998), including the study of the interface between the wall and the sensitive region of the counter. It is shown that the anomalous response observed at large event sizes in the experiment is due to an enhanced entry of secondary electrons from the wall into the gas cavity.     

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.     

ESR spin trapping of hydroxyl radicals in aqueous solution irradiated with high-LET carbon-ion beams

The aim of this study was to quantify the hydroxyl radicals (*OH) produced when aqueous solutions are decomposed by high-linear energy transfer (LET) 290 MeV/nucleon carbon-ion beams using an electron spin resonance (ESR) spectrometer. Aerated cell culture medium containing 200 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was irradiated with doses of 0 to 20 Gy with an LET of 20 to 90 keV/ micro m. We were able to obtain ESR spectra 10 min after irradiation, and the formation of *OH and hydrogen atoms was confirmed by radiolysis of deuterium oxide and ethanol containing DMPO. Our results showed that the yield of *OH by carbon-ion radiolysis increased in proportion to the absorbed dose over the range of 0 to 20 Gy. Furthermore, we discovered that the yield of *OH decreased linearity as LET increased logarithmically from 20 to 90 keV/ micro m. The generation of *OH by carbon-ion radiolysis at LETs of 20, 40, 60, 80 and 90 keV/ micro m was 64, 58, 52, 49 and 50%, respectively, of that for low-LET X radiolysis. These unique findings provide a further understanding of the indirect effect of high-LET radiation.     

Cataractogenic action of accelerated carbon ions with energies of 300 MeV/nucleon

The influence of carbon ions of 300 MeV/nucleon on the incidence of lenticular opacity has been studied on mice. The cataractogenic efficiency of low carbon ion doses (0.003 to 0.5 Gy) is higher than that of gamma-radiation. The threshold dose of carbon ions is 0.05 Gy. The RBE ratios vary from 30.4 to 11.1 as the period of the postirradiation observation increases from 20 to 50 weeks.     

Chromosomal instability and delayed apoptosis in long-term T-lymphocyte cultures irradiated with carbon ions and x rays

In this study, we examined genomic instability induced by 250 kV X rays and 100 MeV/nucleon carbon ions in long-term lymphocyte cultures from two healthy donors. Two biological end points, delayed apoptosis and chromosomal instability, were studied in descendants of cells irradiated with three different doses of the particular radiation up to 22 population doublings. The delayed apoptosis showed no clear dependence on radiation dose, culture time or radiation quality. A persistent significant increase in the rate of apoptosis up to 36 days after X irradiation was observed for a dose of 4 Gy in donor 1 only. For both donors and radiations, de novo aberration yields were significantly increased in comparison to control values up to day 36. For both radiations, chromosome-type aberrations were seen more frequently than chromatid-type aberrations in both donors up to 22 days postirradiation. In both donors, carbon ions were more effective than X rays with respect to the induction of chromosome instability. A dose of 0.25 Gy of carbon ions corresponding to 1.4 ion traversals per cell nucleus was effective in the induction of instability in our cell system.     

Truly incomplete and complex exchanges in prematurely condensed chromosomes of human fibroblasts exposed in vitro to energetic heavy ions

Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon silicon ions, or iron ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 degrees C for 24 h after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Incomplete and complex exchanges were analyzed in the irradiated samples. To verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole-chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after irradiation with the heavy ions of high LET, and consequently the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/microm, the highest LET included in the present study. For samples exposed to 200 MeV/nucleon iron ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique, which allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy iron ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges; these ratios were higher than those obtained after exposure to 6 Gy gamma rays. After 0.7 Gy of iron ions, most complex aberrations were found to involve three or four chromosomes, which is a likely indication of the maximum number of chromosome domains traversed by a single iron-ion track.     

Effects of low dose particle radiation to mouse neonatal neurons in culture.

To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions generated by HIMAC at NIRS and BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis focusing on the dependencies of (1) the animal strains with different radiation sensitivities, and (2) LET with different nuclei. Of the three mouse strains, SCID, B6 and C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to both X-ray and carbon ion ( 290 MeV/n) as evaluated by 10% apoptotic criterion. However, the sensitivity differences among the strains were much smaller in case of carbon ion comparing to that of X-ray. Regarding the LET dependency, the sensitivity was compared with using C3H and B6 cells between the carbon (13 keV/micrometers) and neon (70 keV/micrometers) ions. Carbon (290 MeV/n) did not give a detectable LET dependency from the criterion whereas the neon (400 MeV/n) showed 1.4 fold difference for both C3H and B6 cells. Although a LET dependency was examined by using the most sensitive SCID cells, no significant difference was detected.     

Primary and secondary radiation doses from neon beam fragments

The neon beam at 250 MeV/nucleon from the Bevalac at the Lawrence Berkeley Laboratory is bombarded in nuclear emulsion. The experimental interaction cross section of the neon beam in emulsion is 1078 +/- 35 mb, in agreement with the calculations from the modified Bradt and Peters formula. The secondary fragments were identified and their partial production cross sections were calculated. From the fluences of the primary and secondary fragments, we determine their radiation doses which are presented as a function of depth in the absorber.     

The fragmentation of 670A MeV neon-20 as a function of depth in water. I. Experiment

We present the final analysis of an experiment to study the interaction of a beam of 670A MeV neon ions incident on a water column set to different thicknesses. The atomic number Z (and, in some cases, the isotopic mass A) of primary beam particles and of the products of nuclear interactions emerging from the water column close to the central axis of the beam was obtained for nuclei between Be (Z = 4) and Ne (Z = 10) using a time-of-flight telescope to measure the velocity and a set of silicon detectors to measure the energy loss of each particle. The fluence of particles of a given charge was obtained and normalized to the incident beam intensity. Corrections were made for accidental coincidences between multiple particles triggering the TOF telescope and for interactions in the detector. The background due to beam particles interacting in beam line elements upstream of the detector was calculated. Sources of experimental artifacts and background in particle identification experiments designed to characterize heavy ion beams for radiobiological research are summarized, and some of the difficulties inherent in this work are discussed. Complete tables of absolutely normalized fluence spectra as a function of LET are included for reference purposes.     

Investigation of heavy-ion-induced sucrose radicals by electron paramagnetic resonance

The production of sucrose radicals with heavy-ion irradiation was investigated by an EPR (electron paramagnetic resonance) spectroscopic method. We examined the correlation between the production of sucrose radicals and the ion species, as well as LET (linear energy transfer). The spectral pattern obtained was the same for various ion species, including helium, carbon, neon, argon and iron ions. Quantitative EPR analyses showed that the production of sucrose radicals depended on both the ion species and the LET for the same dose of 50 Gy. The spin yield obtained showed a logarithmic correlation with the LET. In addition, the EPR response had a linear relationship with dose in the dose range of 5-60 Gy. Thus the present EPR results show that sucrose can be used to monitor the ionizing particle based on the radical yield.     

High-LET irradiation of a DNA-binding protein: protein-protein and DNA-protein crosslinks

The chromosomal protein MC1 is a monomeric protein of 93 amino acids that is able to bind any DNA but has a slight preferential affinity for some sequences and structures, like cruciform and minicircles. The protein has been irradiated with 36Ar18+ ions of 95 MeV/nucleon. The LET of these particles in water is close to 270 keV/microm. We tested the activity of the protein by measuring its ability to form complexes with DNA. We tested the integrity of the protein by measuring the molecular weight of the species formed. Compared with gamma radiation, we observed for the same dose a less efficient inactivation of the protein, a greater protection of the protein by the bound DNA, a lower induction of chain breakage, and a greater production of protein-protein and DNA-protein crosslinks. The results are discussed in terms of the quantitative and the qualitative differences between the two types of radiation: The global radical yield is slightly higher with gamma rays, whereas the density of radicals produced along the particle track is considerably higher with argon ions.     

Modeling the effects of low-LET cosmic rays on electronic components

The effects of cosmic radiation in single cells, organic tissues and electronics are a major concern for space exploration and manned missions. Standard heavy ions radiation tests employ ion cocktails with energy of the order of 10 MeV per nucleon and with a linear energy transfer ranging from a few MeV cm(2) mg(-1) to hundreds of MeV cm(2) mg(-1). In space, cosmic rays show significant fluxes at energies up to the order of GeV per nucleon. The present work aims at investigating single event damage due to low-, high- and very-high-energy ions. The European Space Agency reference single event upset monitor data are used to support the discussion. Finally, the effect of ionization induced directly by primary particles and ionization induced by recoils produced in an electronic device is investigated for different types of devices.