The calculation of linear energy transfer, with special reference to a 14 MeV electron beam and 10 MeV per nucleon ion beams.
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Electrons↗
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THE LINEAR ENERGY TRANSFER DISTRIBUTIONS RESULTING FROM PRIMARY AND SCATTERED X-RAYS AND GAMMA RAYS WITH PRIMARY HVL'S FROM 1.25 MM CU TO 11 MM PB.
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Gamma Rays↗
Induction of DNA-protein crosslinks in Chinese hamster V79-4 cells exposed to high- and low-linear energy transfer radiation.
The induction of DNA-protein crosslinks (DPCs) in Chinese hamster V79-4 cells after irradiation under hypoxic and aerobic conditions at 277 K with 60Co gamma rays, 238Pu alpha particles and aluminum K (Al(K)) ultrasoft X rays has been determined using a nitrocellulose filter binding assay. The dose dependences for the induction of DPCs, which involves covalent linkage, are linear over the absorbed dose range used (0-400 Gy with alpha-particle and gamma radiation, 0-600 Gy with Al(K) X rays). The yield of DPCs induced under hypoxic conditions is 55, 51 and 25 DPCs per gray per cell for 60Co gamma rays, alpha particles and Al(K) X rays, respectively. The yield of DPCs is significantly reduced in the presence of oxygen by 20, 50 and 79% for 60Co gamma rays, alpha particles and Al(K) X rays, respectively. Since the mean size of the DNA attached to the protein is uniform for 60Co gamma rays and alpha particles, variations in the DNA size do not influence the yields of DPCs. Although a DPC may be considered as a complex lesion combining two macromolecules, the dependence of the yield of DPCs on LET does not reflect the ionizing density of the radiations used. Further, this dependence on LET and the effect of oxygen do not reflect the corresponding dependences determined for a variety of biological responses. From these findings and knowledge of the radiation tracks, it is proposed that DPCs induced particularly under aerobic conditions with 60Co gamma rays are formed mainly in the sparsely ionizing segments of the radiation track.
Animals↗
The effect of high-linear energy transfer ions on the electron paramagnetic resonance signal induced in alanine.
Microcrystalline samples of L-alanine irradiated with energetic high-LET cobalt and iron ions had different EPR spectra compared to alanine samples irradiated with low-LET photons. The differences in the shapes of the EPR spectra and their dependence on the microwave power are related to the differences in the microwave power saturation of the radicals induced by the various types of ionizing radiation. The changes in the shape of the EPR spectra, which were caused by increasing microwave power, were more pronounced in samples irradiated with low-LET radiation than with high-LET particles. This effect showed a long-term stability and can be used to monitor radiation quality.
Alanine↗
Does the limiting F value at very low doses depend systematically on linear energy transfer?
The debate on the validity of the ratios of radiation-induced yields of chromosome aberrations, in particular the F value (dicentrics/ring chromosomes), as a chromosomal fingerprint of radiation quality is still in progress. From a recent analysis of their experimental data, Sasaki et al. (Radiat. Res. 150, 253-258, 1998) noted that despite a considerable variability in the data, the limiting F value at the lowest doses, or the F(0) value, obviously decreased with increasing LET, indicating that the LET could be a factor that determines the F value. We have reassessed here our own 13 cytogenetic data sets that cover a range of dose-averaged LET of 0.5 to 150 keV/microm in terms of this F(0)-value approach, but we could not confirm such a dependence on LET at very low doses. The validity of the F value as a biomarker therefore remains questionable. For a final evaluation, scoring of a far greater number of cells at low doses would be necessary to reduce the large error ranges of F values.
Cells, Cultured↗
The difference that linear energy transfer makes to precursors of DNA strand breaks.
Using agarose gel electrophoresis, we have measured the yields of DN A single- and double-strand breaks (SSBs and DSBs) for plasmid DNA irradiated in aerobic aqueous solution with either 137Cs gamma rays or 4He ions with a mean LET of 94 or 150 keV micron-1. The presence of dimethyl sulfoxide (DMSO) resulted in a decrease in the yields of both SSBs and DSBs, with a greater decrease being apparent for gamma irradiation than for 4He-ion irradiation. Irradiation by 4He ions in the presence of N-(2-thioethyl)- 1,3-diaminopropane (WR-1065) resulted in a decrease in the yield of SSBs and a slightly larger decrease in the yield of DSBs. Together with results obtained previously, these observations suggest a substantial contribution to the formation of SSBs and DSBs by 4He ions by species containing at least two radicals and more than two radicals, respectively.
DNA Damage↗
The biological effectiveness of radon-progeny alpha particles. II. Oncogenic transformation as a function of linear energy transfer.
Epidemiological studies have established an association between exposure to radon and carcinoma of the lung. However, based on data for either lung cancer in uranium miners exposed to radon or bronchial epithelial carcinomas in Japanese A-bomb survivors, it has not been possible to assign estimates of risk of lung cancer for the general population exposed to radon in their homes. Based on past success with the excellent quantitative properties of the C3H 10T1/2 in vitro oncogenic transformation assay system, the relative biological effectiveness (RBE) for radiation-induced transformation for charged particles of defined LET has been determined. As the LET of the radiation was increased, the rate of induction of oncogenic transformation increased and the RBEm approached 20. At higher LETs, RBE dropped precipitously. The rapid drop in effectiveness for alpha particles with LETs between 120 and 265 keV/microns implies a lower quality factor than the 20-25 currently considered appropriate when estimating lung cancer mortality.
Alpha Particles↗
Joining of correct and incorrect DNA ends at double-strand breaks produced by high-linear energy transfer radiation in human fibroblasts.
DNA double-strand breaks (DSBs) were measured within a 3.2-Mbp NotI fragment on chromosome 21 of cells of a normal human fibroblast cell line. Correct rejoining of DSBs was followed by measuring reconstitution of the original-size NotI fragment, and this was compared to total rejoining as measured by a conventional pulsed-field gel electrophoresis technique (FAR assay). After 80 Gy of particle irradiations with LETs in the range of 7-150 keV/microm, it was found that the repair kinetics was generally slower after irradiation with high-LET particles compared to X irradiation and that a larger proportion of the breaks remained unrepaired after 24 h. On the other hand, the misrejoining frequency as measured by the difference between correct and total rejoining after 24 h did not change with LET, but was approximately the same for all radiations at this dose, equal to 25-30% of the initial breaks. This result is discussed in relation to formation of chromosomal aberrations, deletion mutations and other biological end points.
Cells, Cultured↗
Cellular effects of individual high-linear energy transfer particles and implications for tissue response at low doses.
The energy deposition patterns produced by the radiation environment in space can be quite different from those in conventional radiation environments. Furthermore, conventional radiation biological experiments, using randomly distributed particle tracks, cannot access some variables which may be important in determining the health effects of irradiation. Controlled microbeam irradiation provides the means to investigate the effects and unique energy deposition patterns and cell environment for a variety of end points.
Alpha Particles↗
The merits of cell kinetic parameters for the assessment of intrinsic cellular radiosensitivity to photon and high linear energy transfer neutron irradiation.
PURPOSE: Differences in tumor response and intrinsic cellular radiosensitivity make the selection of patients for specific radiation modalities very difficult. The reasons for these differences are still unclear, but are thought to be due to genomic and cellular characteristics. Because radiosensitivities vary between cell cycle stages and because S phase cells are very radioresistant, cell cycle kinetic parameters could be a candidate for predicting intrinsic radiosensitivity. METHODS AND MATERIALS: A panel of 15 tumor cell lines was analyzed for S phase content and potential doubling times (Tpot), and the influence of these parameters on the intrinsic radiosensitivity to 60Co gamma- and p(66)/Be neutron irradiation was assessed. RESULTS: S phase content and Tpot show a statistically significant correlation with the mean inactivation dose for photons. The correlation between cell kinetic parameters and the mean inactivation dose for neutrons showed the same trend as photon sensitivity but this was not found to be statistically significant. CONCLUSIONS: S phase content and Tpot were identified as suitable criteria for predicting photon sensitivity. It is suggested that cell kinetic parameters could play a role in identifying neutron sensitive tumors if both tumor and normal cells are analyzed.
Cobalt Radioisotopes↗
Genomic instability in Chinese hamster cells after exposure to X rays or alpha particles of different mean linear energy transfer.
Evidence has accumulated that radiation induces a transmissible persistent destabilization of the genome, which may result in effects arising in the progeny of irradiated but surviving cells. An enhanced death rate among the progeny of cells surviving irradiation persists for many generations in the form of a reduced plating efficiency. Such delayed reproductive death is correlated with an increased occurrence of micronuclei. Since it has been suggested that radiation-induced chromosomal instability might depend on the radiation quality, we investigated the effects of alpha particles of different LET by looking at the frequency of delayed micronuclei in Chinese hamster V79 cells after cytochalasin-induced block of cell division. A dose-dependent increase in the frequency of micronuclei was found in cells assayed 1 week postirradiation or later. Also, there was a persistent increase in the frequency of dicentrics in surviving irradiated cells. Moreover, we found an increased micronucleus frequency in all of the 30 clones isolated from individual cells which had been irradiated with doses equivalent to either one, two or three alpha-particle traversals per cell nucleus. We conclude that the target for genomic instability in Chinese hamster cells must be larger than the cell nucleus.
Alpha Particles↗
Induction and rejoining of DNA double-strand breaks in normal human skin fibroblasts after exposure to radiation of different linear energy transfer: possible roles of track structure and chromatin organization.
DNA double-strand breaks are nonrandomly induced by high-LET radiation. Differences in the induction and rejoining of DSBs after irradiation with ions having different LET were detected by fragment analysis. The data obtained indicate that the track structure of the traversing particle and its interaction with the different chromatin structures of the cellular DNA influence the yield as well as the distribution of the induced damage. The induction and rejoining of clustered DSBs induced by the same nitrogen ion fluence at LETs of 80-225 keV/microm were investigated by a detailed analysis of the DNA fragmentation patterns in normal human fibroblasts. The DSBs in the cells were allowed to rejoin during incubations for 0-20 h. Two separate pulsed-field gel electrophoresis protocols were used, optimized for separation of fragments in the size ranges 1-6 Mbp and 5 kbp-1.5 Mbp. A strong influence of LET on the level of DSB induction was evident. The DSB yield increased from 4.5 +/- 0.2 to 10.0 +/- 0.3 DSBs per particle traversal through the cell nucleus when LET increased from 80 to 225 keV/microm. Further, the size distribution of the DNA fragments showed a significant dependence on radiation quality, with an excess of fragments at 50-200 kbp and around 1 Mbp. Differences in repair kinetics were also evident, with slower rejoining for increasing LET, and the initial nonrandom fragment distributions were still present after 1 h of repair.
Chromatin↗
A model of galactic cosmic rays for use in calculating linear energy transfer spectra.
The galactic cosmic rays (GCR) contain fully stripped nuclei, from Hydrogen to beyond the Iron group, accelerated to high energies and are a major component of the background radiation encountered by satellites and interplanetary spacecraft. This paper presents a GCR model which is based upon our current understanding of the astrophysics of GCR transport through interstellar and interplanetary space. The model can be used to predict the energy spectra for all stable and long-lived radioactive species from H to Ni over an energy range from 50 to 50,000 MeV/nucleon as a function of a single parameter, the solar modulation level phi. The details of this model are summarized, phi is derived for the period 1974 to present, and results from this model during the 1990/1991 CRRES mission are presented.
Cosmic Radiation↗
Genetic and cytogenetic markers of exposure to high-linear energy transfer radiation.
It has been suggested that the more closely spaced, clustered DNA breaks seen with high-LET radiations are more likely to result in chromosome intrachanges than in chromosome interchanges. We determined whether analysis of the spectra of chromosome aberrations or Hprt gene mutations in CHO-K1 cells could detect a shift to more chromosome intrachanges and therefore distinguish exposure to high-LET radiation from exposure to low-LET radiation, and whether alterations in the processing of DNA breaks would influence this process. Both the frequency and type of chromosome aberrations and Hprt gene mutations were determined in CHO-K1 and xrs-5 cells exposed to 60Co gamma rays or 212Bi alpha particles. Xrs-5 cells are a radiosensitive derivative of CHO-K1 cells that are defective in rejoining of DNA double-strand breaks. The ratio of dicentrics to centric rings (F ratio) was significantly lower in CHO-K1 and xrs-5 cells exposed to alpha particles, consistent with a shift to more chromosome intrachanges with higher LET. In contrast, the frequency of large interstitial deletions at the Hprt locus, determined by multiplex polymerase chain reaction-based exon deletion analysis, was the same for both gamma-ray- and alpha-particle-exposed cells in each of the cell lines. Thus the F ratio can distinguish high-LET from low-LET radiations, and the end point is not influenced by differences in the processing of DNA double-strand breaks. The analysis of the spectrum of Hprt mutations, however, appears unable to discriminate low LET from high LET.
Alpha Particles↗
In vitro screening for synergism of high-linear energy transfer 213Bi-radiotherapy with other therapeutic agents for the treatment of B-cell chronic lymphocytic leukemia.
BACKGROUND: External beam radiotherapy and beta-radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha-emitters is attractive, owing to the high (LET) nature and short path length of alpha particles allowing for higher tumor cell kill and lower toxicity to healthy tissues. OBJECTIVES: The aim of this study was to assess the response of B-Cell chronic lymphocytic leukemia (B-CLL) cells in vitro after treatment with chemotherapy (cisplatin, fludarabine, doxorubicin, or vincristine) or other pharmaceuticals (colchicine, simvastatin, or cyclosporin A) in combination with (60)Co-gamma or (213)Bi-alpha-irradiation. METHODS: (213)Bi was eluted from a (225)Ac generator. Apoptosis was scored by flow cytometric analysis of the cells stained with Annexin-V and 7 amino actinomycin D. Metabolic activity was assessed by a MTT assay. RESULTS: The response induced by alpha- irradiation is systematically higher than the response induced by gamma-irradiation. The combination of drug treatment with alpha-irradiation induced a systematic, higher response, compared to treatment with drugs alone, even for the highest concentrations used. For all the drugs used in this study, synergism or additivity was demonstrated for the combination of drugs and radiotherapy with a stronger effect for alpha-particles. CONCLUSIONS: The results of this in vitro study highlight a potential benefit of alpha-irradiation in combination with the drugs considered in this study.
Alpha Particles↗
Effects of high linear energy transfer radiation on the cochlea of C3H/He mouse during postnatal developmental course.
To investigate the biological effectiveness of neutrons at energies below 1MeV with regard to ear toxicity, we exposed mice to 1.0 Gy of monoenergetic neutrons (1.026 MeV) or 137Cs gamma rays at 7 days of age, and observed subsequent morphological changes in the inner ear with light and scanning electron microscopes. Monoenergetic neutrons, but not gamma rays, caused acute changes in the ear. The epithelium of the greater epithelial ridge in the organ of Corti showed degeneration around 6 hours and disappeared by 72 hours post-irradiation. The apoptotic cell death of the epithelium of the greater epithelial ridge was inducible by the radiation at 3 or 4 days of age. The hair cells formed the protrusion structures of the surface by 72 hours post-irradiation. Neutron-irradiation also caused acute otitis media until 10 weeks of age.
Aging↗
Monte Carlo simulation of the production of short DNA fragments by low-linear energy transfer radiation using higher-order DNA models.
A realistic DNA target model has been developed and implemented in the biophysical simulation code PARTRAC. It describes five levels of the B-DNA structure (nucleotides, DNA helices, nucleosomes, chromatin fiber structure and chromatin fiber loops) on an atomic level for the whole genome inside a mammalian cell nucleus. The model is capable of describing regular solenoidal, crossed-linker or zigzag structures as well as repeating stochastic arrangements of nucleosomes in the chromatin fiber. Electron tracks resulting from monoenergetic electrons with energies up to 100 keV and from 220 kVp X rays, starting at random positions in the cell, were superimposed on four DNA target models with different chromatin fiber structures. The yields of SSBs, DSBs and short single- and double-stranded DNA fragments were determined from spatial coincidences with strand atoms. Two parameters of the model-the energy necessary to create an SSB and the distance between two breaks that would be scored as a DSB-were adapted to equate simulated and measured strand break yields after X irradiation of human fibroblast cells. The integral fractions of short single- and double-stranded fragments were rather similar for all condensed chromatin fiber structures; they agreed with experimental data for DNA fragments below 2 kbp. The simulated fragment size distributions in the range from 0.1 to 1.5 kbp reflected the fiber structure irrespective of strandedness or electron energy. The distributions using a stochastic arrangement of nucleosomes in the chromatin fiber were found to be in better accordance with experimental data than those obtained with regular fiber structures.
DNA↗
Radiation-induced cell death by chromatin loss. A model to explain the shape of low-linear-energy-transfer cell survival curves.
A model is proposed which relates reproductive death of cells caused by radiation to loss of chromatin at cell division. This loss of chromatin can occur through chromosomal deletions or through the formation of asymmetrical chromosomal exchanges. It is proposed that smaller doses of radiation produce fewer chromatin breaks, which are more likely to be accurately repaired, compared with larger doses. Consequently, smaller doses of radiation are less efficient in causing cell death, leading to a shoulder on the cell survival curve. Experimental evidence supports this model, and the fit between the derived formula and experimental cell survival curves is good. The derived formula approximates to the linear-quadratic equation at low doses of radiation.
Cell Division↗