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PubMed1998

Effects of melanin on high- and low- linear energy transfer (LET) radiation response of human epithelial cells.

The search for effective radioprotectors is of major concern in the medical, military, environmental, and space sciences. Conventional radioprotectors are generally effective only during a single irradiation and display their radioprotective properties only at high, toxic concentrations. In addition, they reduce somatic radiation effects but are poorly efficient in protecting from hereditary stochastic radiation effects. In this respect, the pigment melanin merits attention. Experiments referring to potential melanin effects on the ionising radiation response have been carried out with different biological systems, both in vivo and in vitro. In this paper, we present results on the response to high- and low-linear energy transfer (LET) radiation of a human mammary epithelial cell line, H184B5 F5-1 M/10, supplemented by melanin. The incorporation of auto-oxidative (L-dopa) melanin was linear for concentrations from 3 to 10 micrograms/ml in the growth medium. Concentrations of up to 250 micrograms/ml did not significantly impair the cells proliferative ability. No significant protective effect of melanin on the survival of cultured cells after exposure to alpha-particles (130 keV/micron) or x-rays was observed.

Alpha Particles↗
PubMed1998

Depth dependence of absorbed dose, dose equivalent and linear energy transfer spectra of galactic and trapped particles in polyethylene and comparison with calculations of models.

A matched set of five tissue-equivalent proportional counters (TEPCs), embedded at the centers of 0 (bare), 3, 5, 8 and 12-inch-diameter polyethylene spheres, were flown on the Shuttle flight STS-81 (inclination 51.65 degrees, altitude approximately 400 km). The data obtained were separated into contributions from trapped protons and galactic cosmic radiation (GCR). From the measured linear energy transfer (LET) spectra, the absorbed dose and dose-equivalent rates were calculated. The results were compared to calculations made with the radiation transport model HZETRN/NUCFRG2, using the GCR free-space spectra, orbit-averaged geomagnetic transmission function and Shuttle shielding distributions. The comparison shows that the model fits the dose rates to a root mean square (rms) error of 5%, and dose-equivalent rates to an rms error of 10%. Fairly good agreement between the LET spectra was found; however, differences are seen at both low and high LET. These differences can be understood as due to the combined effects of chord-length variation and detector response function. These results rule out a number of radiation transport/nuclear fragmentation models. Similar comparisons of trapped-proton dose rates were made between calculations made with the proton transport model BRYNTRN using the AP-8 MIN trapped-proton model and Shuttle shielding distributions. The predictions of absorbed dose and dose-equivalent rates are fairly good. However, the prediction of the LET spectra below approximately 30 keV/microm shows the need to improve the AP-8 model. These results have strong implications for shielding requirements for an interplanetary manned mission.

Cosmic Radiation↗
PubMed1996

Small doses of high-linear energy transfer radiation increase the radioresistance of Chinese hamster V79 cells to subsequent X irradiation.

Chinese hamster V79 cells show a complex X-ray survival response which is characterized by hypersensitivity followed by increased resistance as the dose increases to 1 Gy. This hypersensitivity can be eliminated by pretreating cells with X rays or hydrogen peroxide. Accordingly, the protective effect that results from the priming treatments could be considered analogous to the "adaptive response" induced by low-linear energy transfer (LET) radiation and some chemical agents in human lymphocytes. Indeed, no hyper-radiosensitive response after single treatments in V79 cells or adaptive response in human lymphocytes has been reported after exposure to high-LET radiation. To investigate this further, we measured the survival after X irradiation of V79-379A cells previously irradiated with small priming doses of high-LET radiation. After a 0.2-Gy priming dose of neutrons followed by a 1-Gy 250 kVp X-ray dose given 4 h later, survival was 1.08 +/- 0.04 compared to 0.73 +/- 0.03 when the doses were given concurrently. Increases in survival were also observed from 0.80 +/- 0.03 to 0.96 +/- 0.05 after a 0.2-Gy priming treatment with 250 kVp X rays and from 0.78 +/- 0.03 to 0.84 +/- 0.03 with a priming dose of Bragg-peak negative pi mesons. The results indicate that a protective effect, as measured by an increase in radioresistance, is induced by high-LET neutrons, as well as by Bragg-peak pi mesons and X rays, and that a threshold level of damage is required for adaptation to occur.

Adaptation, Physiological↗
PubMed1997

DNA complex lesions induced by protons and alpha-particles: track structure characteristics determining linear energy transfer and particle type dependence.

The yield of DNA double-strand breaks (dsb) and DNA complex lesions induced by protons and alpha-particles of various energies was simulated using a Monte Carlo track structure code (MOCA15) and a simple model of the DNA molecule. DNA breaks of different complexity were analysed. The linear energy transfer (LET) and particle-type dependence of lesions of higher complexity seems to confirm the importance of clustered damage in DNA as a relevant step leading to biological endpoints such as cell inactivation. The detailed structure of proton and alpha-particle tracks was analysed to identify the main characteristics possibly responsible for such a dependence. The role of the primary ion and of its secondary electrons in inducing dsb and complex lesions is described, showing that the relative contribution of secondary electron tracks alone in inducing clustered lesions is almost negligible at high LET, but tends to dominate below = 10 keV/micron. This is consistent with the observed similar effectiveness of low-LET fast particle radiation and sparsely ionizing radiation such as x-rays. The dependence on LET and particle type is mainly due to energy deposition events of the primary ion together with short range electrons surrounding the ion track; the yield of complex lesions due to secondary electron tracks alone is substantially LET independent. The radial distributions of the energy contributing to the induction of complex lesions were analyzed and compared with the radial distributions of energy deposition of the full tracks. The results suggest that the stochastic behaviour (i.e. cluster properties) of the energy deposition pattern within a radius of a few nanometers around the ion track plays a relevant role in determining the biological radiation effectiveness.

Alpha Particles↗
PubMed2000

A comparison of depth dependence of dose and linear energy transfer spectra in aluminum and polyethylene.

A set of four tissue-equivalent proportional counters (TEPCs), with their detector heads at the centers of 0 (bare), 3, 7 and 9-inch-diameter aluminum spheres, were flown on Shuttle flight STS-89. Five such detectors at the centers of polyethylene spheres were flown 1 year earlier on STS-81. The results of dose-depth dependence for the two materials convincingly show the merits of using material rich in hydrogen to decrease the radiation exposure to the crew. A comparison of the calculated galactic cosmic radiation (GCR) absorbed dose and dose-equivalent rates using the radiation transport code HZETRN with nuclear fragmentation model NUCFRG2 and the measured GCR absorbed dose rates and dose-equivalent rates shows that they agree within root mean square (rms) error of 12.5 and 8.2%, respectively. However, there are significant depth-dependent differences in the linear energy transfer (LET) spectra. A comparison for trapped protons using the proton transport code BRYNTRN and the AP-8 MIN trapped-proton model shows a systematic bias, with the model underpredicting dose and dose-equivalent rates. These results show the need for improvements in the radiation transport and/or fragmentation models.

Aluminum↗
PubMedDate not supplied

On the use of effective dose in the treatment planning of high linear-energy-transfer radiation.

Treatment planning for conventional radiations is based on the assumption that the effect of a combination of doses at any location in the treatment field in a multibeam plan will be equivalent to that of a single dose made up of the total sum of the doses delivered to that location. This is obviously valid for conventional low linear-energy-transfer (LET) radiations when the dose contributions from various beam components are associated with the same relative biological effectiveness (RBE) value of unity. However, this is not the case for the new generation of charged particle beams whose RBEs have been shown to vary significantly with depth. A concept of effective dose, defined as the mathematical product of physical dose and RBE value evaluated for an effect level, is developed for the treatment planning of these high-LET particle radiations. Based on radiobiological results in mixed radiation experiments, it is shown that these effective doses are linearly additive like physical doses and hence, can be used directly for general treatment planning using linear algorithms already developed for the use of physical doses. This is illustrated using examples of simplified one-dimensional plans for the TRIUMF pion beam.

Biometry↗
PubMed2005

A comparison of high- versus low-linear energy transfer somatostatin receptor targeted radionuclide therapy in vitro.

INTRODUCTION: The somatostatin analog [DOTA(0)-Tyr(3)]-octreotide (DOTATOC) has been widely used to target somatostatin receptor expressing tumors for therapy using radionuclides such as (90)Y or (177)Lu. AIM: This aim of this study was to compare the effects of DOTATOC labeled to high linear energy transfer (LET) alpha-emitter (213)Bi and low-LET beta-emitter (177)Lu in vitro. MATERIALS AND METHODS: Somatostatin receptor (sstr)-positive cell line Capan-2 and sstr-negative control cell line A549 were used for the experiments. The effects of two exposure times using different radiation doses of high-LET alpha-emitter (213)Bi and low-LET beta-emitter (177)Lu were investigated using cell survival assay. The apoptotic effects were investigated using Cell Death Detection ELISA(PLUS)10x. The cumulated activity and the mean absorbed dose per unit cumulated activity were calculated using MIRD cellular Svalues. RESULTS: (213)Bi-DOTATOC had an approximately four times greater induction of apoptosis than (177)Lu-DOTATOC and a 100 times greater induction of apoptosis than nonradiolabeled DOTATOC. Nonspecific radiolabeled tetra-azacyclododecanetetra-acetic acid (DOTA) had a less pronounced effect on the cell survival and apoptosis, as compared to the sstr-specific radiolabeled DOTATOC. CONCLUSION: (213)Bi-DOTATOC is significantly more potent than (177)Lu-DOTATOC in vitro because of its high-LET alpha-emission.(213)Bi-DOTATOC shows enhanced effects on mitotic and apoptotic cell deaths.

Actinium↗
PubMed1992

Amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of linear energy transfer and dose.

The c-myc oncogene was previously shown to be amplified in large, later-stage carcinomas of the rat skin induced by 0.8-MeV electrons. In a panel of 70 tumors induced by neon ions (45 keV/microns), c-myc amplification was rare, and in contrast to the data for tumors induced by low-linear-energy transfer (LET) (0.3 keV/microns) radiation, showed no correlation with tumor size, growth period, or time, but was associated with radiation dose. The tissue specificity for c-myc amplification seen in tumors induced by electrons was not seen in tumors induced by neon ions. These results suggest that quite distinct molecular mechanisms operate even in late stages of carcinogenesis that depend on the LET of the inducing radiation. Furthermore, the results suggest that c-myc amplification observed in tumors induced by low-LET radiation is not a general property of rat skin carcinomas, but is linked mechanistically to the inducing radiation, even though it is not detectable until many months after exposure and tumor appearance.

Animals↗
PubMed1991

Comments on radiation dosimetry and linear energy transfer.

The quantification of the physical effects of ionizing radiation in human tissue is the basis of risk assessment. This quantification results from determination of kerma or absorbed dose. The procedure for the absolute determination of absorbed dose with an ionization chamber is discussed. The biological effects of ionizing radiation are dependent, not only on the absorbed dose but also on a second physical parameter, the linear energy transfer.

Energy Transfer↗
PubMed1991

Relationship between linear energy transfer and behavioral toxicity in rats following exposure to protons and heavy particles.

Rats were exposed to protons (155 MeV) or to helium (165 MeV/amu), neon (522 MeV/amu) or argon (670 MeV/amu) particles to evaluate the behavioral toxicity of these types of radiations. Behavioral toxicity was assessed using the conditioned taste aversion paradigm. Exposure to all types of radiation produced dose-dependent increases in the intensity of the acquired taste aversion. However, the intensity of the aversions, measured as the dose that produced a 50% decrease in the intake of the sucrose-conditioned stimulus, did not show significant variation as a function of the linear energy transfer (LET) of the radiation. The results are discussed in terms of the relationship between LET and behavioral toxicity.

Animals↗
PubMed1992

A spatially restricted linear energy transfer equation.

An analytical expression is developed for calculating the average energy deposited by an ion in a volume with dimensions less than the range of the secondary electrons produced. The expression is obtained by including two additional terms in an energy-restricted linear-energy-transfer equation. The usual energy-restricted expression accounts for energy deposited in the volume by energy transfers less than a certain cutoff value. The modified expression, due to the two additional terms, also accounts for energy deposited in the volume which results from energy transfers greater than the cutoff value. The additional terms therefore convert the energy-restricted equation to a distance- or spatially restricted equation. The method is used to obtain radial dose profile information on ion tracks and to calculate the energy deposited by an ion randomly incident upon spherical and hemispherical target sites. Results are in close agreement with more complex methods reported previously for ions with energies from 0.25 to 1000 MeV/amu in volumes of water vapor with dimensions from 1 nm to 10 microns. There are no fitted parameters in this general approach, and all the necessary input data are readily available.

Energy Transfer↗
PubMed1994

Dose conversion factors and linear energy transfer for irradiation of thin blood layers with low-energy X rays.

For irradiation of thin samples of biological material with low-energy X rays, conversion of measured air kerma, free in air to average absorbed dose to the sample is necessary. In the present paper, conversion factors from measured air kerma to average absorbed dose in thin blood samples are given for four low-energy X-ray qualities (14-50 kVp). These factors were obtained by Monte Carlo simulation of a practical sample holder. Data for different thicknesses of the blood and backing layer are presented. The conversion factors are found to depend strongly on the thicknesses of the blood layer and backing layer. In radiobiological work, knowledge of linear energy transfer (LET) values for the radiation quality used is often required. Track-averaged LET values for low-energy X rays are presented in this work. It is concluded that the thickness of the sample does not influence the LET value appreciably, indicating that for all radiobiological purposes this value can be regarded as a constant throughout the sample. Furthermore, the large difference between the LET value for a 50 kV spectrum found in this work and the value given in ICRU Report 16 is pointed out.

Blood↗