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[Experimental studies of the relative biological effectiveness of accelerated charged particles varying in energy].

Experimental results and literary data were analyzed for the relative biological effectiveness of heavy charged particles in a broad range of energy and LET to cells of humans and other mammals in culture, whole body of laboratory animals, microorganisms, bacteriophages, and plants. Analyzed were data obtained with the use of a diversity of tests of acute and delayed lesions induced by ionizing radiation, cancers and cataracts, specifically. Non-parametric methods are applied in parallel to the classic method of calculating the coefficients of relative biological effectiveness by correlating the equal-effective doses of the standard and a given radiation. Consideration is given to factors that may modify RBE values estimated for different types of radiation.

Animals↗

A review of high LET facilities, existing and projected, with emphasis on the radiobiologic aspects.

The introduction of high LET radiations into radiotherapy is an exciting development. Neutron facilities are already in clinical use in England and the United States, while machines to produce negative pi mesons and high energy heavy ions are in an advanced stage of development in Canada, the United States and Europe. The state of the art at each of these installations is reviewed. The therapeutic merits of various heavy particles are compared with conventional photon beams. Lowering the OER (oxygen enhancement ratio) and improvement in the depth dose pattern are the principal advantages sought. Neutrons result in a somewhat lower OER but offer depth-dose patterns that are barely the equal of x- and gamma-rays. Protons by contrast produce excellent dose distributions, but no reduction of OER. Negative pi mesons improve both depth dose pattern and OER to some extent. High energy heavy nuclei show the greatest promise as far as lowering the OER is concerned, but will probably not equal pions in depth dose pattern. More radiobiologic data are urgently needed for all of these new radiation modalities.

Canada↗

Absorbed dose rate estimation for protons, leptons and helium observed with AMS01 experiment in low earth orbit during STS-91 mission.

The Alpha Magnetic Spectrometer (AMS01), a high-sensitivity particle spectrometer, was successfully flown for 10 d in June 1998 (STS91) in the orbit of the International Space Station (51.7 degrees, -380 km). A high-statistics dataset of galactic cosmic rays were measured as a function of geomagnetic latitude, including the primary protons, leptons and helium as well as the trapped and quasi-trapped proton and lepton components. In this paper, the absorbed dose rate owing to the protons, leptons and helium are presented and compared with measurements made by other instruments flown on the same mission.

Body Burden↗

Single track effects, Biostack and risk assessment.

The scientific career of Prof. Bucker has spanned a very exciting period in the fledgling science of Space Radiation Biology. The capability for placing biological objects in space was developed, and the methods for properly packaging, retrieving and analyzing them were worked out. Meaningful results on the effects of radiation were obtained for the first time. In fact, many of the successful techniques and methodologies for handling biological samples were developed in Prof. Bucker's laboratories, as attested by the extensive Biostack program. He was the first to suggest and successfully carry out experiments in space directly aimed at measuring effects of single tracks of high-energy heavy galactic cosmic rays by specifically identifying whether or not the object had been hit by a heavy particle track. Because the "hit" frequencies of heavy galactic cosmic rays to cell nuclei in the bodies of space travelers will be low, it is expected that any effects to humans on the cellular level will be dominated by single-track cell traversals. This includes the most important generally recognized late effect of space radiation exposure: radiation-induced cancer. This paper addresses the single-track nature of the space radiation environment, and points out the importance of single "hits" in the evaluation of radiation risk for long-term missions occurring outside the earth's magnetic field. A short review is made of biological objects found to show increased effects when "hit" by a single heavy charged-particle in space. A brief discussion is given of the most provocative results from the bacterial spore Bacillus subtilis: experimental evidence that tracks can affect biological systems at much larger distances from the trajectory than previously suspected, and that the resultant inactivation cross section in space calculated for this system is very large. When taken at face value, the implication of these results, when compared to those from experiments performed at ground-based accelerators with beams at low energies in the same LET range, is that high-energy particles can exert their influence a surprising distance from their trajectory and the inactivation cross sections are some 20 times larger than expected. Clearly, beams from high-energy heavy-ion accelerators should be used to confirm these results. For those end points that can also be caused by low-LET beams such as high-energy protons, it is important to measure their action cross sections as well. The ratio of the cross sections for a high-LET beam to that of a low-LET beam is an interesting experimental ratio and, we suggest, of more intrinsic interest than the RBE (Relative Biological Effectiveness). It is a measure of the "biological" importance of one particle type relative to another particle type. This ratio will be introduced and given the name RPPE (Relative Per Particle Effectiveness). Values of RPPE have appeared in the literature and will be discussed. A rather well-known value of this quantity (13,520) has been suggested for the RPPE of high-energy iron ions to high-energy protons. This value was suggested by Letaw et al. Nature 330, 709-710 (1987)] we will call it the Letaw limit. It will be discussed in terms of the importance of the heavy-ion component vs light-ion component of the galactic cosmic rays. It is also pointed out, however, that there may be unique effects from single tracks of heavy ions that do not occur from light-ion tracks. For such effects, the concepts of both RBE and RPPE lose their meaning.

Bacillus subtilis↗

Monte Carlo track structure studies of energy deposition and calculation of initial DSB and RBE.

Estimation of exposure due to environmental and other sources of radiations of high-LET and low-LET is of interest in radiobiology and radiation protection for risk assessment. To account for the differences in effectiveness of different types of radiations various parameters have been used. However, the relative inadequacy of the commonly used parameters, including dose, fluence, linear energy transfer, lineal energy, specific energy and quality factor, has been made manifest by the biological importance of the microscopic track structure and primary modes of interaction. Monte Carlo track structure simulations have been used to calculate the frequency of energy deposition by radiations of high- and low-LET in target sizes similar to DNA and higher order genomic structure. Tracks of monoenergetic heavy ions and electrons were constructed by following the molecular interaction-by-interaction histories of the particles down to 10 eV. Subsequently, geometrical models of these assumed biological targets were randomly exposed to the radiation tracks and the frequency of energy depositions obtained were normalized to unit dose in unit density liquid water (l0(3) kg m-3). From these data and a more sophisticated model of the DNA, absolute yields of both single- and double-strand breaks expressed in number of breaks per dalton per Gray were obtained and compared with the measured yields. The relative biological effectiveness (RBE) for energy depositions in cylindrical targets has been calculated using 100 keV electrons as the reference radiation assuming the electron track-ends contribution is similar to that in 250 kV X-ray or Co60 gamma-ray irradiations.

Aluminum↗

In vivo radiobiology of heavy ions.

The radiobiology of heavy charged particles has been investigated with various animal systems in vivo at the Lawrence Berkeley Laboratory using the helium beam from the 184" synchrocyclotron and the carbon, neon, and argon beams from the BEVALAC. Tumor experiments were carried out using the R1 sarcoma in rats and the EMT6 mouse mammary carcinoma, comparing X rays, carbon ions, neon ions, and argon ions. In vivo normal tissue experiments have been carried out with a wide range of tissues including testis, bone marrow, intestinal crypt cells, lens of the eye, esophagus, lung, and the spinal cord. The induction of dominant lethal mutations after irradiation of the testis was assayed by in vitro embryo culture after in vivo irradiation. Experiments were also done with the Harderian gland tumor induction system.

Animals↗

Chronic effects of neutrons and charged particles on spinal cord, lung, and rectum.

The effects of multifraction irradiation with X rays, neutrons, and pions on the rat cervical and lumbar spinal cord, mouse lung, and rat rectum have been investigated. The linear-quadratic model was used to analyze the effectiveness per unit dose for various tissue responses. It is concluded that the dependence of tolerance doses on fraction size is considerably reduced for both intermediate (pions) and high-LET (neutrons) radiations, as shown by the observed alpha/beta ratios in the range of 20-50. With accurately defined alpha/beta values for various tissues and types of radiation, the same tolerance formalisms can be used as proposed for low-LET radiation. The effectiveness of pion irradiation shows a significant dependence on dose rate when treatment times are long and repair of subeffective damage occurs during the irradiations. For late effects in spinal cord, lung, and rectum, RBE values of pions are 1.5 or less at doses per fraction in the range of 1.2-4.5 Gy.

Animals↗

Induced radioactivities in concrete constituents irradiated by high-energy particles.

The powdered concrete constituents of magnetite ore, pyrites ore, marble, gravel and Portland cement were prepared and irradiated by 12- GeV protons and secondary particles at the slow extracted beam line of the National Laboratory for High Energy Physics ( KEK ) 12- GeV proton synchrotron. The saturated activities for individual nuclides produced were calculated, and the time variation of photon exposure rate due to the residual activities was also evaluated for each sample. The exposure rates ranked in the following order: magnetite ore greater than pyrites ore greater than gravel greater than or equal to cement greater than marble. The levels of photon exposure rates from heavy, ordinary and marble concretes were also estimated on the basis of the results obtained for each constituent. It is suggested that the use of marble concrete in the inside wall of accelerator tunnels can reduce considerably the exposure to the accelerator maintenance workers, compared with heavy and ordinary concretes commonly used.

Construction Materials↗

Sources of fine particulate matter in personal exposures and residential indoor, residential outdoor and workplace microenvironments in the Helsinki phase of the EXPOLIS study.

OBJECTIVES: This study assessed the source contributions to the mass concentrations of fine particles (PM2.5) in personal exposures and in residential indoor, residential outdoor, and workplace indoor microenvironments of the nonsmoking adult population unexposed to environmental tobacco smoke in Helsinki, Finland. METHODS: The elemental composition of 48-hour personal exposure and residential indoor, residential outdoor, and workplace indoor PM2.5 was analyzed by energy-dispersive X-ray fluorescence spectrometry for 76 participants not exposed to environmental tobacco smoke and 102 participating residences with no smoking in Helsinki as a part of the EXPOLIS study. Subsequently, a principal component analysis was used to identify the emission sources of PM2.5-bound elements and black smoke in each microenvironment, and this information was used to identify the corresponding sources in personal exposures. Finally, source reconstruction was done to determine the relative contributions of each source type to the total PM2.5 mass concentrations. RESULTS: Inorganic secondary particles, primary combustion, and soil were the dominant source types for the PM2.5 mass concentration in all the microenvironments and personal exposures. The ratio of the residential indoor-to-outdoor PM2.5 concentration was close to unity, but the corresponding elemental ratios and source contributions varied. Resuspension of soil dust tracked indoors was a much larger contributor to residential and workplace indoor PM2.5 than soil dust to residential outdoor PM2.5. Source contributions to personal PM2.5 exposures were best approximated by data from residential and workplace indoor microenvironments. CONCLUSIONS: Population exposure assessment of PM2.5, based on outdoor fixed-site monitoring, overestimates exposures to outdoor sources like traffic and long-range transport and does not account for the contribution of significant indoor sources.

Adult↗

Heavy charged particle irradiation of human cancers.

One of the attractive areas of radiation oncological research is the study of improved local and regional control of resistant tumors through delivery of more effective radiation therapy. A number of potentially useful modalities are under study including combinations of debulking surgery and radiotherapy, chemotherapy and radiotherapy, hypoxic cell sensitizers and radiotherapy, hyperthermia, and multiple daily fractionation of photon irradiation. Radiotherapy with pions, helium and heavier charged particles have several advantageous characteristics for accomplishing this goal. At the University of California Lawrence Berkeley Laboratory (LBL) we have been studying the use of radiotherapy with helium and heavier charged particles which have several advantageous characteristics for delivery of cancerocidal therapy to deep seated tumors. These include greater localization of the radiation dose to the target volume as well as potentially greater tumor cell-killing potency relative to normal cell damage: A significant lessening of the radiation protective effect of hypoxia on tumor cells may be expected when radiation exposures are made with ions heavier than atomic number 10. Heavy ions also depress enzymatic repair mechanisms, decrease variations in radiosensitivity during the cell division cycle, cause greater than expected delay in cell division and decrease the protective effects of neighbouring cells in organized systems. A potential clinical advantage may result from irradiation with heavy ions in the atomic number range of 10-15 if a significant difference in the above parameters can be found between normal tissues and tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗

Radiotherapy by particle beams (hadrontherapy) of intracranial tumours: a survey on pathology.

A review of the principal contributions of radio-therapy of brain tumours by beam particles is carried out. Neutrons, protons and light ions are considered along with their pros and cons in relation to types and locations of brain tumours. A particular emphasis is given to the pathologic studies of their effects directly o n tumours and on the normal nervous tissue, considering mainly the relevant action mechanisms of the radiation types and the requirements of the clinical therapeutic strategies. For comparison the main features of the pathologic effects of radiotherapy by photons are described. From the review it emerges that the new modality of radiation by protons and light ions, because of their peculiar physical characteristics, may represent a new way of destroying the tumour and sparing normal nervous tissue, especially when deeply located and irregularly shaped tumours are concerned. More neuropathological studies are needed in order to better understand the potentiality of the new treatment of modalities.

Adult↗

Dose and LET distributions due to neutrons and photons emitted from stopped negative pions.

Computer calculations are made of the dose and LET distributions due to neutrons and photons produced when negative pions are stopped in a phantom. When negative pions are stopped in a material they undergo nuclear capture, resulting in the disintegration of the nucleus and the emission of short range charged particles and longer range neutrons and photons. The uncharged radiation constitutes a potentially large source of dose outside the treatment volume. A simple phantom consisting of a 0-25 m cube of either tissue or bone-equivalent material is set up with a 0-05 m cube in the centre to represent the treatment volume. Neutrons and photons are started in this central volume and transported across the phantom using Monte Carlo transport codes. Several different initial energy spectra for the neutrons are used, taken from experimental and theoretical data. These different spectra are found to give significant differences in dose, though the distance to the 80% dose level is always about 0-015 m. Order of magnitude differences in some LET regions are also found. The dose deposited by neutrons in bone is about 24% less than in soft tissue, the photon dose being small compared with the neutron dose.

Elementary Particles↗

Recent measurements for hadrontherapy and space radiation: nuclear physics.

The particles and energies commonly used for hadron therapy overlap the low end of the charge and energy range of greatest interest for space radiation applications, Z=1-26 and approximately 100-1000 MeV/nucleon. It has been known for some time that the nuclear interactions of the incident ions must be taken into account both in treatment planning and in understanding and addressing the effects of galactic cosmic ray ions on humans in space. Until relatively recently, most of the studies of nuclear fragmentation and transport in matter were driven by the interests of the nuclear physics and later, the hadron therapy communities. However, the experimental and theoretical methods and the accelerator facilities developed for use in heavy ion nuclear physics are directly applicable to radiotherapy and space radiation studies. I will briefly review relevant data taken recently at various accelerators, and discuss the implications of the measurements for radiotherapy, radiobiology and space radiation research.

Cosmic Radiation↗

Measurements of n-p correlations in the reaction of relativistic neon with uranium.

We report a preliminary measurement of coincident neutron-proton pairs emitted at 45 degrees in the interaction of 400, 530, and 650 MeV/A neon beams incident on uranium. Charged particles were identified by time of flight and momentum, as determined in a magnetic spectrometer. Neutral particles were detected using a thick plastic scintillator, and their time of flight was measured between an entrance scintillator, triggered by a charged particle, and the neutron detector. The scatter plots and contour plots of neutron momentum vs. proton momentum appear to show a slight correlation ridge above an uncorrelated background. The projections of this plane on the n-p momentum difference axis are essentially flat, showing a one standard deviation enhancement for each of the three beams energies. At each beam energy, the calculated momentum correlation function for the neutron-proton pairs is enhanced near zero neutron-proton momentum difference by approximately one standard deviation over the expected value for no correlation. This enhancement is expected to occur as a consequence of the attractive final state interaction between the neutron and proton (i.e., virtual or "singlet" deuterons). The implications of these measurements are discussed.

Elementary Particles↗

Radiation dosimetry using three-dimensional optical random access memories.

The ability to determine particle type and energy plays an important role in the dosimetry of heavy charged particles (HCP) and neutrons. A new approach to radiation dosimetry is presented, which is shown to be capable of particle type and energy discrimination. This method is based on utilising radiation induced changes in the digital information stored on three-dimensional optical random access memories (3D ORAM). 3D ORAM is a small cube (a few mm3) composed of poly(methyl methacrylate) doped with a photochromic dye. and it was originally proposed as a memory device in high speed parallel computers. A Nd:YAG laser system is used to write and read binary information (bits) on the ORAM, which functions as a charged particle detector. Both the read and the write processes use two laser beams that simultaneously strike the material to cause a colour change at their intersection (similar to the darkening of light-sensitive sunglasses when exposed to sunlight.) The laser produces colour changes in the ORAM, which then reverts to the original colour ('bit-flips') at sites where energy is deposited from interaction with incident HCP or neutron-recoil protons. The feasibility of this approach was demonstrated both theoretically and experimentally. Calculations based on track structure theory (TST) predict that when HCP interact with the ORAM material, the local energy deposition is capable of inducing measurable 'bit-flips'. These predictions were recently confirmed experimentally using two types of ORAM systems, one based on spirobenzopyran and the other on anthracene, as the photochromic dyes.

Computer Storage Devices↗

Experimental and calculated LET distributions in the Cosmos-2044 biosatellite orbit.

During the flight of the Cosmos-2044 biosatellite, joint U.S.S.R.-U.S.A. investigations of different characteristics of cosmic radiation (CR) in the near-Earth environment were carried out. The U.S. dielectric track detectors CR-39 and Soviet BYa- and BR-type nuclear photo-emulsions were used as detectors. The present work shows some results of experimental measurements of linear energy transfer (LET) spectra of CR particles obtained with the use of these detectors, which were placed both inside and outside the satellite. The LET spectra measurement with plastic detectors is composed of two parts: the measurement of galactic cosmic rays (GCR) particles, and of short-range particles. The contributions of these components to the total LET distribution at various thicknesses of the shielding were analyzed and the results of these studies are presented. Calculated LET spectra in the Cosmos-2044 orbit were compared with experimental data. On the basis of experimental and calculated values of the LET spectra, absorbed and equivalent CR doses were calculated. In the shielding range of 1-1.5 g cm-2, outside the spacecraft, the photo-emulsions yielded 10.3 mrad d-1 and 27.5 mrem d-1 (LET > or = 2 MeV cm-1) while the CR-39 yielded averages of 1.43 mrad d-1 and 13.4 mrem d-1 (LET > or = 40 MeV cm-1). Inside the spacecraft (> or = 10 g cm-2) the photo-emulsions yielded 8.9 mrad d-1 and 14.5 mrem d-1.

Cosmic Radiation↗

Biomedical program leading to therapeutic trials on pion radiation at Los Alamos.

Hypoxia and variations in cell cycle phase protect tumor cells being treated with x rays or gamma rays (cobalt). Heavy particles can overcome these protective effects, because of the dense ionization they deposit in tissues. Pions (negative pi mesons) can be directed to and stopped in a specific area, where they are captured by the nuclei of atoms, rendering the nuclei unstable. The nuclei disintegrate, releasing densely ionizing radiation. By confining the dense ionization to the tumor-bearing volume, pions have the potential of increasing the tolerance of the area under treatment to radiation, thus increasing the probability of destroying the tumor. A special channel at the proton factory at the Los Alamos Scientific Laboratory is producing pions for biomedical research. Considerable physical dosimetry has been completed. Cellular studies are underway to provide depth-dose-biological-effect curves. Animal studies will provide information on acute and late effects, which will permit the safe application of pions to a series of anatomical sites established by protocols for radiotherapy clinical trials.

Animals↗

Beta decay and the origin of biological chirality: new experimental results.

The proposed connection between the parity-violating handedness of beta particles in radioactive decay and the sign (L) of biological chirality (the Vester-Ulbricht [V-U] hypothesis) is being investigated by measuring the theoretically predicted asymmetry in the formation of triplet positronium in amino acid enantiomers by low energy positrons under reversal of the helicity of the positrons. We find the asymmetry in leucine to be (0.8 +/- 1.0) X 10(-4), i.e. consistent with the theoretical prediction of 10(-6) to 10(-7). The apparatus is now sensitive enough to test the predicted asymmetry in optically active molecules which have heavy atoms at their chiral centers. The connection between these results and asymmetry in radiolysis by beta-decay electrons is made, and the implications of our limits for the V-U hypothesis discussed. Although the above limits are 10(6) times lower than direct measurements of radiolysis, they are still not small enough to allow us to rule out the V-U hypothesis.

Elementary Particles↗