Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Linear Energy Transfer”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1995

On the revised concept of linear energy transfer.

The quantities linear energy transfer or restricted linear energy transfer are utilized in calculations that link absorbed dose to the fluence distribution of a radiation field. The computations provide approximations to absorbed dose in terms of the intermediate quantity cema or reduced cema. With the definition of the restricted linear energy transfer, L delta, given in ICRU Report 33, the approximation remains imperfect. This study deals with the resulting need for a modified definition of L delta, as proposed in a draft report of ICRU. Essential differences between the old and the new definitions are demonstrated. The changed definition permits a rigorous formulation of the dependence between fluence and absorbed dose.

Dose-Response Relationship, Radiation↗
PubMed2002

Reduction of survival and induction of chromosome aberrations in tobacco irradiated by carbon ions with different linear energy transfers.

PURPOSE: To determine the relationship between linear energy transfer (LET) and the relative biological effectiveness (RBE) for survival reduction and chromosome aberration induction in plants. MATERIALS AND METHODS: Tobacco seeds were exposed to carbon ions having LET ranging from 92 to 260 keV microm(-1). Survival ratc was determined at 7 weeks after sowing. Chromosome aberrations were observed when the root length reached about 0.5 mm (immediately after radicle emergence), 3 and 10 mm. RESULTS: The RBE for both endpoints increased with increasing LET and showed the highest value at 230 keV um(-1). The highest RBE was 65.0 for survival reduction and 52.5 for chromosome aberration induction. The types and yield ratio of chromosome aberrations such as fragments and bridges were not affected by radiation type at 0.5mm root length. As the roots elongated from 0.5 to 10 mm, the frequency of aberrant cells gradually decreased. The number of cells with fragments decreased faster than the number of cells with bridges. The decrement of chromosome aberrations appeared to be slower in roots irradiated by carbon ions than in roots irradiated by gamma-rays. CONCLUSIONS: The results show a close relationship between survival reduction and chromosome aberration induction in plants. The types and yield ratio of initial chromosome aberrations did not differ among gamma-rays and carbon ions with different LET.

Carbon↗
PubMed1996

Cellular and molecular analysis of mutagenesis induced by charged particles of defined linear energy transfer.

Mutation induction by charged particles of defined linear energy transfer (LET) and gamma rays was scored using human-hamster hybrid AL cells. The LET values for charged particles accelerated at the Radiological Research Accelerator Facility ranged from 10 keV/microm protons to 150 keV/microm 4He ions. The induced mutant fractions at both the S1 and HGPRT loci were dependent on the dose and LET. In addition, for each dose examined, the mutant yield at the S1 locus was 30-60 fold higher than at the corresponding HGPRT locus. To determine whether the mutation spectrum was comparably dependent on dose and LET, independent S1- and HGPRT- mutants induced by 150 keV/microm 4He ions and gamma rays were isolated, and their DNA was analyzed by both Southern blotting and multiplex PCR methods. While the majority of radiation-induced mutants showed deletions of varying sizes, the relative percentage of large deletions was found to be related to both the dose and LET of the radiation examined. Using a mutation system that can detect multilocus changes, results of the present study show that radiation-induced chromosomal loss can be in the millions of base pairs.

Animals↗
PubMed1984

Current status of high linear energy transfer irradiation.

Based on laboratory investigations, high linear energy transfer (LET) particle irradiation is capable of more efficient cell kill than that associated with conventional or low LET irradiation. The advantages of high LET irradiation include: (1) a greater ability to damage hypoxic cells; (2) a lesser ability for repair of sublethal and potentially lethal radiation-induced damage; (3) less variation in radiation sensitivity relative to the cell cycle; and (4) a greater ability to deposit the radiation dose in the region of the tumor as opposed to the normal surrounding tissue (neutrons do not have this advantage compared to other particle therapy). Despite these laboratory advantages, it has been difficult to demonstrate any advantage of high LET irradiation in the clinic. A number of new developments have occurred to test the role of high LET: (1) sophisticated technology to enable treatment delivery with higher dose rate and improved depth dose; (2) the construction of hospital-based facilities; and (3) the development of randomized studies involving diseases in which the risk of early metastasis is minimized. It is hoped that careful study in the clinic over the next decade will elucidate the role of high LET particle therapy.

Clinical Trials as Topic↗
PubMed1988

Mutation induction by charged particles of defined linear energy transfer.

The mutagenic potential of charged particles of defined linear energy transfer (LET) was assessed using the hypoxanthine-guanine phosphoribosyl transferase locus (HGPRT) in primary human fibroblasts. Exponentially growing cultures of early passaged fibroblasts were grown as monolayers on thin mylar sheets and were irradiated with accelerated protons, deuterons or helium-3 ions. The mutation rates were compared with those generated by 137Cs gamma-rays. LET values for charged particles accelerated at the Radiological Research Accelerator Facility, using the track segment mode, ranged from 10 to 150 keV/micron. After irradiation, cells were trypsinized, subcultured and assayed for both cytotoxicity and 6-thioguanine resistance. For gamma-rays, and for the charged particles of lower LET, the dose-response curves for cell survival were characterized by a marked initial shoulder, but approximated to an exponential function of dose for higher LETs. Mutation frequencies, likewise, showed a direct correlation to LET over the dose range examined. Relative biological effectiveness (RBE) for mutagenesis, based on the initial slopes of the dose-response curves, ranged from 1.30 for 10 keV/micron protons to 9.40 for 150 keV/micron helium-3 ions. Results of the present studies indicate that high-LET radiations, apart from being efficient inducers of cell lethality, are even more efficient in mutation induction as compared to low-LET ionizing radiation. These data are consistent with results previously obtained with both rodent and human fibroblast cell lines.

Cell Survival↗
PubMed1990

Linear energy transfer (LET) spectra of cosmic radiation in low Earth orbit.

Integral linear energy transfer (LET) spectra of cosmic radiation (CR) particles were measured on five Cosmos series spacecraft in low Earth orbit (LEO). Particular emphasis is placed on results of the Cosmos 1887 biosatellite which carried a set of joint U.S.S.R.-U.S.A. radiation experiments involving passive detectors that included thermoluminescent detectors (TLDs), plastic nuclear track detectors (PNTDs), fission foils, nuclear photo-emulsions, etc. which were located both inside and outside the spacecraft. Measured LET spectra are compared with those theoretically calculated. Results show that there is some dependence of LET spectra on orbital parameters. The results are used to estimate the CR quality factor (QF) for the Cosmos 1887 mission.

Cosmic Radiation↗
PubMed1988

Radiosensitization produced by iododeoxyuridine with high linear energy transfer heavy ion beams.

Little is known about radiosensitization produced by iododeoxyuridine (IUDR) with high linear energy transfer radiation. Likewise, the effect of IUDR on repair of sublethal or potentially lethal damage is unclear. A series of in vitro experiments was performed examining these aspects of IUDR radiosensitization. Human T1 cells were grown in the presence of 3.0 micromolar IUDR for 72 hours (approximately three doubling times), an exposure which resulted in minimal cytotoxicity to unirradiated cells. As the cells entered plateau phase they were exposed to X rays and a variety of heavy ion beams. Sensitization was found to decrease as linear energy transfer (LET) increased. No sensitization took place in an extremely high LET Lanthanum ion beam (1000 keV/micrometer). However, IUDR produced significant sensitization in the Neon ion beam currently used to treat cancer patients at Lawrence Berkeley Laboratory. Sensitization enhancement ratios at the 40% cell survival level were found to be 1.8 for X rays, 1.5 for the proximal Bragg peak of the clinical Neon beam, and 1.3 for the distal peak of the clinical Neon beam. Cell survival curves fitted to the linear-quadratic model showed IUDR significantly increased the value of the linear component (alpha) in beams with LETs below 40 keV/micron. The value of the quadratic component (beta) was unaffected by IUDR, regardless of LET. Split-dose experiments with both X rays and proximal peak Neon ions revealed IUDR did not affect sublethal damage repair. Similarly, delayed-plating experiments showed IUDR did not affect repair of potentially lethal damage. In contrast to cells unexposed to IUDR, IUDR-treated cells showed near-equal levels of cell killing throughout the extended Bragg peak of the clinical Neon beam. These findings suggest that the addition of IUDR to Neon ion radiotherapy could enhance the therapeutic ratio of the clinical Neon beam.

Cell Survival↗
PubMed2000

DNA damage induced by radiation of different linear energy transfer: initial fragmentation.

PURPOSE: To investigate DNA fragmentation as a function of linear energy transfer (LET) after exposure to accelerated ions in the LET range 40-225 keV/microm. MATERIALS AND METHODS: Fragmentation patterns of double-stranded DNA in the range 5 kilobasepairs (kbp) to 5.7 megabasepairs (Mbp) were analysed after irradiation of low-passage GM 5758 normal human fibroblast cells with 60Co-photons, helium ions at 40 keV/microm and high-LET nitrogen ions between 80 and 225 keV/microm. Two separate pulsed-field gel electrophoresis protocols were used, optimized for separation of 1-6 Mbp and 5 kbp to 1.5 Mbp fragments. RESULTS: An increased probability of formation of short and medium-sized DNA fragments was revealed following high-LET irradiation. The DNA double-strand break (dsb) induction yields were, respectively, 5.8 and 6.9-8.8 x 10(-9) dsb bp(-1) Gy(-1) for 60Co-photons and ions. The ion yields were some 80-110% higher than those calculated according to a conventional approach, disregarding the fragment distributions. For photons, the yield was 13% higher. The corresponding relative biological effectiveness (RBE) of dsb induction was in the range 1.2-1.5. CONCLUSIONS: A significant non-random contribution to the number of dsb after irradiation with high-LET was confirmed by detailed fragment analysis using pulsed-field gel electrophoresis. The LET had a strong influence on the initial DNA fragment distribution, and hence also on the induction yields measured. However, when the LET was increased to the highest values studied for nitrogen ions, the yield decreased slightly.

Cells, Cultured↗
PubMed1991

Increased nuclear damage by high linear energy transfer radioisotopes applicable for radiodirected therapy against radiologic malignancies.

High linear energy transfer radioisotopes carried by appropriate agents have been proposed for receptor-directed radiotherapy. Two such classes of isotopes are Auger electron and alpha-emitting nuclides. To determine the relative cytotoxicity and nuclear damage to cells produced by these two classes of nuclides, we compared bromine-80m (80mBr), an Auger-electron-emitting radionuclide with a 4.4-hour half-life, with bismuth-212 (212Bi), an alpha-emitter with a 1-hour half-life. Because of the short path length of the Auger electrons, 80mBr was radiotoxic only when incorporated into DNA, such as in the form of [80mBr]bromodeoxyuridine ([80mBr]BrUdR). Both agents induced linear increases in chromosome aberration frequency, however, [80mBr]BrUdR caused multiple aberrations including the shattering of parts of the chromosomes. While, in contrast, a 2-hour exposure of cells to 212Bi, chelated to DTPA, a form which does not enter the cell, induced much less extensive chromosome damage. Exposure to equivalent activities of Auger electrons or alpha-particles results in 5 times more damage in Auger-electron-exposed cells. However, estimates of dose suggest they are equally toxic. Unlike Auger electrons, alpha-particles did not need to be in as close proximity to the DNA to have clastogenic and radiotoxic effects.

Alpha Particles↗
PubMed2001

[Production of superoxide radicals with pulse radiolysis of water with high linear energy transfer].

The radiolysis of water with heavy ions of high linear energy transfer (LET) (-dE/dx) is characterized, in deaerated medium, by the production of superoxide anions, the radiolytic yields of which increase with the LET. Radiobiological interest in such radical species comes from the oxidative stress which may be generated by their dismutation in O2 and H2O2 in anoxic medium (radiotherapy with heavy ions). A brief review of the measurements of superoxide free radicals in aqueous solution by indirect or direct methods is presented. Moreover, some experimental results obtained by pulse radiolysis with Ar18+ ions (TEL = 290 keV x microm(-1)), are described. The interpretation of the kinetics takes into account the superoxide absorbance and that of hydrogen peroxide, which is present at the millisecond time scale.

Algorithms↗
PubMed2003

Analytical linear energy transfer calculations for proton therapy.

As the relative biological effectiveness of protons depends on the linear energy transfer (LET), simple methods for LET calculations are desired for the optimization of proton therapy. This work provides an analytical model for the LET on the central axis of broad proton beams in water, which can also be applied to spread-out Bragg peaks. For realistic treatment situations with polyenergetic beams, the LET is here defined as a local mean of the proton stopping power, weighted by the local energy spectrum. The proposed model considers only Coulomb interactions and neglects nonelastic nuclear interactions. By assuming a Gaussian shape for the energy spectrum and by using a suitable parametrization of the stopping power, analytical expressions for the track averaged and the dose averaged LET are derived, which account for range straggling as well as for the initial width of the energy spectrum. The analytical model was evaluated by Monte Carlo simulations with GEANT 3.21. Local energy spectra were simulated to obtain LET distributions for several cases, using clinical energies between 70 and 250 MeV and varying widths of the initial energy spectrum. Good agreement was found between the analytical model and the Monte Carlo simulations (with maximum deviations of 0.5 keV per micrometer), which justifies the assumptions used in the derivation of the analytical model.

Body Burden↗
PubMed2000

Rejoining of DNA fragments produced by radiations of different linear energy transfer.

PURPOSE: To analyse the rejoining of DNA double-strand breaks (dsb) produced by high-linear energy transfer (LET) ions, with the specific focus on the influence, on the rejoining estimates, of the way dsb are distributed along chromosomes. MATERIAL AND METHODS: Low passages of normal human fibroblasts (GM5758) were irradiated with 60Co photons, 40 keV/microm helium ions or nitrogen ions with LETs of 80, 125, 175 and 225 keV/microm. The double-stranded DNA fragment distributions, ranging from 5 kbp to 5.7 Mbp, were assayed by pulsed-field gel electrophoresis after repair incubation for 0-22 h. RESULTS: The rejoining was biphasic and the half-times of the two phases were 15 min and 2-3h, respectively, and were independent of LET. Although the majority of breaks were rejoined by the fast phase, both the fraction of dsb rejoined by the slow phase and the fraction of unrejoined dsb at 20-22h increased with increasing LET. CONCLUSIONS: DNA fragment analysis detected LET-dependent differences in the amount of rejoining while the half-times were independent of LET. The majority of dsb were rapidly rejoined even after high-LET irradiation. If fragment-size distribution is not taken into account, both the fraction of breaks rejoined by slow kinetics, and the fraction of unrejoined breaks, can be overestimated when the LET is increased.

Cells, Cultured↗
PubMed1994

Radially restricted linear energy transfer for high-energy protons: a new analytical approach.

Radially restricted linear energy transfer (LET) is a basic physical parameter relevant to radiation biology and radiation protection. In this report a convenient method is presented for the analytical computation of this quantity without the need for complicated simulation. The method uses the energy-restricted LET L delta, as recently redefined in a 1993 ICRU draft document and supplements it by a relatively simple term that represents the energy of fast delta rays lost within distance r from the track core. The method provides a better fit than other models and is valid over the entire range of radial distance from track center to the maximum radial distance traveled by the most energetic secondary electrons. Lr computed by this approach differs only a few percent from the values obtained from explicit Monte Carlo simulations. The concept applies equally to heavy ions and to electrons.

Linear Energy Transfer↗
PubMed1998

Cell death induced by high-linear-energy transfer carbon beams in human glioblastoma cell lines.

The cytotoxic effect of high-linear-energy transfer (LET) carbon beams on two human glioblastoma cell lines (A172 and TK1) was analyzed, especially concerning cell death, including apoptosis. Gamma-ray radiation was used for comparison. The results of standard colony formation assay showed that the survival fraction of each cell line decreased in an LET-dependent manner. The results of other direct cytotoxic assays, dye exclusion test, and lactate dehydrogenase (LDH) release assay, also displayed a similar relationship between the cytotoxic effect of carbon beams and LET. The maximum values of the cell death index (CDI) were 50.2% in A172 and 37.5% in TK1, both obtained on day 7 after exposure to carbon beams of 80 keV/microm. Apoptosis was observed only on days 4 and 7 after carbon beam irradiation, with maximum values of 7% in A172 and 4.5% in TK1, and the induction of apoptosis after high-LET radiation could be p53-independent. This indicated that a combination of multiple assays to detect cell death was important in evaluating the radiosensitivity of tumor cells, because this approach could more precisely reflect the clinical effectiveness of radiotherapy.

Apoptosis↗
PubMed1975

Survival of synchronized Chinese hamster cells exposed to radiation of different linear-energy transfer.

Chinese hamster V79 cells were exposed to ionizing radiations of a wide range of linear-energy transfer (LET), including 145kV x-rays and six different heavy ions accelerated in the Berkeley heavy-ion linear accelerator. The LET of the ions ranged from 19 keV/um to 2000 keV/um. Survival curves were determined for both synchronized and asynchronous cells, using survival of colony-forming capacity as the end-point. Results with asynchronous cultures were similar to results reported previously for mammalian cells. There was increased effectiveness of killing per dose with increased LET until a change in shape of the single-cell survival curves resulted, from sigmoidal to exponential, with carbon ions (LET of 190 keV/um). With heavier ions, exponential curves were obtained, but with decreased effectiveness per unit dose. Synchronized cultures were obtained by mitotic selection. The expected Chinese hamster cell-cycle survival curve variation was found for X-rays, mainly reflecting the variation in the single-cell extrapolation number, with late S-phase cells the most resistant to radiation. When synchronized cultures were irradiated with the heavy ions that produce exponential survival curves; the survival curves were independent of the cell-cycle time of irradiation. With radiations of LET values between the low and high extremes, a reduced cell-cycle survival curve variation was found, indicating a gradual reduction in the cell-cycle survival curve variation as a function of increased LET.

Animals↗
PubMed1994

A statistical theory of cell killing by radiation of varying linear energy transfer.

A theory is presented that provides an explanation for the observed features of the survival of cultured cells after exposure to densely ionizing high-linear energy transfer (LET) radiation. It starts from a phenomenological postulate based on the linear-quadratic form of cell survival observed for low-LET radiation and uses principles of statistics and fluctuation theory to demonstrate that the effect of varying LET on cell survival can be attributed to random variation of dose to small volumes contained within the nucleus. A simple relation is presented for surviving fraction of cells after exposure to radiation of varying LET that depends on the alpha and beta parameters for the same cells in the limit of low-LET radiation. This relation implies that the value of beta is independent of LET. Agreement of the theory with selected observations of cell survival from the literature is demonstrated. A relation is presented that gives relative biological effectiveness (RBE) as a function of the alpha and beta parameters for low-LET radiation. Measurements from microdosimetry are used to estimate the size of the subnuclear volume to which the fluctuation pertains.

Cell Death↗
PubMed1996

Measurements of the linear energy transfer spectra on the Mir orbital station and comparison with radiation transport models.

A tissue equivalent proportional counter designed to measure the linear energy transfer spectra (LET) in the range 0.2-1250 keV/micrometer was flown in the Kvant module on the Mir orbital station during September 1994. The spacecraft was in a 51.65 degrees inclination, elliptical (390 x 402 km) orbit. This is nearly the lower limit of its flight altitude. The total absorbed dose rate measured was 411.3 +/- 4.41 microGy/day with an average quality factor of 2.44. The galactic cosmic radiation (GCR) dose rate was 133.6 microGy/day with a quality factor of 3.35. The trapped radiation belt dose rate was 277.7 microGy/day with an average quality factor of 1.94. The peak rate through the South Atlantic Anomaly was approximately 12 microGy/min and nearly constant from one pass to another. A detailed comparison of the measured LET spectra has been made with radiation transport models. The GCR results are in good agreement with model calculations; however, this is not the case for radiation belt particles and again points to the need for improving the AP8 omni-directional trapped proton models.

Brazil↗
PubMed2002

Induction of apoptosis by high linear energy transfer radiation: role of p531.

The involvement of the tumor suppressor p53 gene in the sensitivity of many cell types towards low linear energy transfer (LET) radiation is now well established. However, little information is available on the relationship between p53 status of tumor cells and their ability to undergo apoptosis following exposure to high-LET radiation. Here we present the results of experiments carried out with the human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV), carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the occurrence of apoptosis, determined by the quantification of hypodiploid particles as well as the activation of several caspases, was compared with their sensitivity towards high-LET radiation. Results indicate that p53 is involved in the response of TK6 cells to fast neutrons and carbon ions, as measured by cell proliferation and occurrence of apoptosis. However, p53-deficient cells are still able to undergo apoptosis following irradiation. This suggests that heavy ions and fast neutrons induce cellular damage that is not under the control of p53. The involvement of executioner caspases in high-LET radiation induced apoptosis was also evaluated by use of specific inhibitors.

Apoptosis↗