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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↗
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↗
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↗
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↗
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↗
PubMed1997

Dependence of induction of interphase death of Chinese hamster ovary cells exposed to accelerated heavy ions on linear energy transfer.

Induction of interphase death was examined in Chinese hamster ovary cells exposed to accelerated heavy ions (carbon, neon, argon and iron) of various linear energy transfers (LETs) (10-2000 keV/microm). The fraction of cells that underwent interphase death was determined by observing individual cells with time-lapse photography (direct method) as well as by counting cells undergoing interphase death made visible by the addition of caffeine (indirect method). After exposure to X rays, interphase death increased linearly with dose above a threshold of about 10 Gy, whereas it increased at a higher rate without a threshold after exposure to high-LET heavy ions. The relative biological effectiveness (RBE) compared to X rays, as determined at the 50% level of induction, increased with LET, reached a maximum at an LET of approximately 230 keV/microm and then decreased with further increase in LET. The range of LET values corresponding to the maximum RBE appears to be narrower for interphase death than for reproductive death (120-230 keV/microm), as assayed using loss of colony-forming ability as a criterion. The inactivation cross section for interphase cell death reached a plateau of 5-10 microm2. This means that the probability for the induction of interphase death by traversal of a single heavy-ion track through the nucleus (size: about 130 microm2) is about 0.04-0.08.

Animals↗
PubMed1987

Critical values of linear energy transfer, dose rates and doses for radiation hormesis.

Estimates are given of the critical values of linear energy transfer (LET), dose rate and dose, below which radiation hormesis is likely to occur but above which it is unlikely to occur. The critical value of LET is estimated to be 15 congruent to 20 keV/micron, and hence radiation hormesis may occur with beta, gamma or x rays, but is unlikely to occur with alpha radiation. The critical value of dose rate is estimated to be 1 congruent to 10 mGy d-1 for the lifetime exposure, but could be higher than this value for the short period exposure. These estimates are consistent with experimental data. The critical value of dose is also estimated, but cannot be compared with experiment because of lack of data. Brief comparison of plants with animals is made, and it is suggested that the value of the critical dose rate for plants in dry conditions, such as seeds or bulbs, could be higher than the above estimate by about a factor 1000. Some sociological considerations are also given.

Animals↗
PubMed1993

The inverse dose-rate effect for oncogenic transformation by charged particles is dependent on linear energy transfer.

Mouse C3H 10T1/2 cells were exposed to single or fractionated doses of charged particles of defined linear energy transfer (LET) from 25 to 200 keV/microns. Dose fractionation with prolonged time intervals enhanced the yield of transformed foci compared with a single acute dose for a range of LET values between 40 and 120 keV/microns. Radiations of lower or higher LET did not show the enhancement that is commonly referred to as the inverse dose-rate effect. The fractionation scheme that was used consisted of three dose fractions; the maximum enhancement of transformation occurred with an interval of 150 min between dose fractions. This inverse dose-rate effect, demonstrated for cycling cells in log phase, was not seen for cells in plateau phase.

Animals↗
PubMed1994

Evidence against the "oxygen-in-the-track" hypothesis as an explanation for the radiobiological low oxygen enhancement ratio at high linear energy transfer radiation.

Oxygen sensitizes cells toward the effect of ionizing radiation. This sensitization, quantified by the oxygen enhancement ratio (OER), decreases with increasing ionization density or linear energy transfer (LET) of the radiation applied. One explanation for the decreased OER at high LET offers the "oxygen-in-the-track" hypothesis. It claims that oxygen is produced in the track of densely ionizing particles providing an oxic microenvironment around the relevant cellular target molecules, even if cells are exposed under anoxic atmospheric conditions. Experimental evidence is presented against this hypothesis. It is based on the different kinetic pattern of DNA double-strand-break rejoining observed in yeast cells exposed under oxic or anoxic conditions to 3.5 MeV alpha-particles.

DNA↗
PubMed1998

Effect of high linear energy transfer radiation on biological membranes.

Cellular membranes are vital elements, and their integrity is extremely essential for the viability of the cells. We studied the effects of high linear energy transfer (LET) radiation on the membranes. Rabbit erythrocytes (1 x 10(7) cells/ml) and microsomes (0.6 mg protein/ml) prepared from liver of rats were irradiated with 7Li ions of energy 6.42 MeV/u and 16O ions of energy 4.25 MeV/u having maximum LET values of 354 keV/microm and 1130 keV/microm, respectively. 7Li- and 16O-induced microsomal lipid peroxidation was found to increase with fluence. The 16O ions were more effective than 7Li ions, which could be due to the denser energy distribution in the track and the yield of free radicals. These findings suggested that the biological membranes could be peroxidized on exposure to high-LET radiation. Inhibition of the lipid peroxidation was observed in the presence of a membrane-active drug, chlorpromazine (CPZ), which could be due to scavenging of free radicals (mainly HO* and ROO*), electron donation, and hydrogen transfer reactions. The 7Li and 16O ions also induced hemolysis in erythrocytes. The extent of hemolysis was found to be a function of time and fluence, and showed a characteristic sigmoidal pattern. The 16O ions were more effective in the lower fluence range than 7Li ions. These results were compared with lipid peroxidation and hemolysis induced by gamma-radiation.

Animals↗
PubMed1998

Lethality of high linear energy transfer cosmic radiation to Escherichia coli DNA repair-deficient mutants during the 'SL-J/FMPT' space experiment.

We investigated the lethal and mutagenic effects of high linear energy transfer cosmic radiation on 11 strains of Escherichia coli, including DNA repair-deficient mutants, using the Radiation Monitoring Container and Dosimeter in the space shuttle 'Endeavour' as part of the 'SL-J/FMPT' space experiment, the 'Fuwatto '92' project. After the return to earth of the shuttle, we evaluated survival and mutations of samples in space and matched controls. The surviving fractions were determined by means of colony count on broth agar plates, and the mutation frequencies were estimated by appearance of arg' revertants on minimal agar plates. The average of the total equivalent dose rate during this space flight was 0.202 mSv/day as measured by the plastic radiation detectors and the thermoluminescent dosimeters in the Radiation Monitoring Container and Dosimeter. The combined action of DNA polymerase and 3'-->5' exonuclease activities was found to make the greatest contribution to the repair of cosmic radiation-induced DNA damage, 5'-->3' exonuclease and recombination repair enzyme activities made a moderate contribution, whereas UV endonuclease activity was not involved in this DNA repair process.

Colony Count, Microbial↗
PubMedDate not supplied

Measurement of dose distributions of linear energy transfer in matter irradiated by fast neutrons.

A detector has been developed and used to measure dose distributions versus linear energy transfer to thin gas targets in spherical geometry from fast neutron irradiation of tissue-equivalent plastic and carbon. The detector is a hemispherical proportional counter with a Cs(T1) scintillator at the center of the hemisphere. The coincidence of the proportional counter signals constrain the measurements to charged particles traversing the radius of the hemisphere. The charged particle energy deposition distributions are directly measured for a known pathlength. The A-150 kerma factor was measured at a neutron energy of 14.8 MeV and is in agreement with tabulated values. The carbon kerma factor measurements are less than the tabulated value at 14.8 MeV. The alpha-particle production in carbon was measured for neutron energies from 14.1 to 14.8 MeV and is compared with existing data.

Energy Transfer↗