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Mutation induction in bacteria after heavy ion irradiation

From a compilation of experimental data on the mutagenic effects of heavy ions in bacteria, main conclusions have been drawn as follows: (1) The mutagenic efficacy of heavy ions in bacteria depends on physical and biological variables. Physical variables are the radiation dose, energy and charge of the ion; the biological variables are the bacterial strain, the repair genotype of bacteria, and the endpoint investigated (type of mutation, induction of enzymes related to mutagenesis); (2) The responses on dose or fluence are mainly linear or linear quadratic. The quadratic component, if found for low LET radiation, is gradually reduced with increasing LET; (3) At low values of Z and LET the cross section of mutation induction sigma m (as well as SOS response, sigma sos. and lambda phage induction, sigma lambda versus LET curves can be quite consistently described by a common function which increases up to approximately 100 keV/mu m. For higher LET values, the sigma(m) versus LET curves show the so-called 'hooks' observed also for other endpoints; (4) For light ions (Z is less than or equal to 4), the cross sections mostly decrease with increasing ion energy, which is probably related to the decrease of the specific energy departed by the ion inside the sensitive volume (cell). For ions in the range of Z = 10, sigma(m) is nearly independent on the ion energy. For heavier ions (Z is greater than or equal to 16), sigma(m) increases with the energy up to a maximum or saturation around 10 MeV/u. The increment becomes steeper with increasing atomic number of the ion. It correlates with the increasing track radius of the heavy ion; (5) The mutagenic efficiency per lethal event changes slightly with ion energy, if Z is small indicating a rough correlation between cellular lethality and mutation induction, only. For ions of higher Z this relation increases with energy, indicating a change in the 'mode' of radiation action from 'killing-prone' to 'mutation-prone'; and (6) Repair genotype substantially influences the radiation induced mutagenesis. Different mechanisms of mutation induction and/or different types of biologically significant lesions in wild type cells compared to repair deficient strains are a likely explanation.

Horneck, G.↗

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

Kim, Myung-Hee Y.↗

Proton and heavy ion acceleration facilities for space radiation research

The particles and energies commonly used for medium energy nuclear physics and heavy charged particle radiobiology and radiotherapy at particle accelerators are in the charge and energy range of greatest interest for space radiation health. In this article we survey some of the particle accelerator facilities in the United States and around the world that are being used for space radiation health and related research, and illustrate some of their capabilities with discussions of selected accelerator experiments applicable to the human exploration of space.

NASA Discipline Radiation Health↗

Forward production of protons in relativistic 12C-nucleus collisions

The production of protons in heavy ion collisions through the knockout mechanism (abrasion) is described using the Glauber model. The multiple knockouts from the projectile, including the inelastic collision series with the target, are considered using a closure approximation in treating energy conservation. Calculations for reactions of 12C projectiles with several targets at energies of 1 and 2A GeV arc compared to experiments. For large secondary proton momentum a strong dependence on the target mass is found and attributed to multiple scattering of the projectile knockouts.

NASA Discipline Radiation Health↗

Computer Model Of Fragmentation Of Atomic Nuclei

High Charge and Energy Semiempirical Nuclear Fragmentation Model (HZEFRG1) computer program developed to be computationally efficient, user-friendly, physics-based program for generating data bases on fragmentation of atomic nuclei. Data bases generated used in calculations pertaining to such radiation-transport applications as shielding against radiation in outer space, radiation dosimetry in outer space, cancer therapy in laboratories with beams of heavy ions, and simulation studies for designing detectors for experiments in nuclear physics. Provides cross sections for production of individual elements and isotopes in breakups of high-energy heavy ions by combined nuclear and Coulomb fields of interacting nuclei. Written in ANSI FORTRAN 77.

Wilson, John W.↗

Galactic Cosmic Ray Event-Based Risk Model (GERM) Code

This software describes the transport and energy deposition of the passage of galactic cosmic rays in astronaut tissues during space travel, or heavy ion beams in patients in cancer therapy. Space radiation risk is a probability distribution, and time-dependent biological events must be accounted for physical description of space radiation transport in tissues and cells. A stochastic model can calculate the probability density directly without unverified assumptions about shape of probability density function. The prior art of transport codes calculates the average flux and dose of particles behind spacecraft and tissue shielding. Because of the signaling times for activation and relaxation in the cell and tissue, transport code must describe temporal and microspatial density of functions to correlate DNA and oxidative damage with non-targeted effects of signals, bystander, etc. These are absolutely ignored or impossible in the prior art. The GERM code provides scientists data interpretation of experiments; modeling of beam line, shielding of target samples, and sample holders; and estimation of basic physical and biological outputs of their experiments. For mono-energetic ion beams, basic physical and biological properties are calculated for a selected ion type, such as kinetic energy, mass, charge number, absorbed dose, or fluence. Evaluated quantities are linear energy transfer (LET), range (R), absorption and fragmentation cross-sections, and the probability of nuclear interactions after 1 or 5 cm of water equivalent material. In addition, a set of biophysical properties is evaluated, such as the Poisson distribution for a specified cellular area, cell survival curves, and DNA damage yields per cell. Also, the GERM code calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle in a selected material. The GERM code makes the numerical estimates of basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at the NASA Space Radiation Laboratory (NSRL) for the purpose of simulating space radiation biological effects. In the first option, properties of monoenergetic beams are treated. In the second option, the transport of beams in different materials is treated. Similar biophysical properties as in the first option are evaluated for the primary ion and its secondary particles. Additional properties related to the nuclear fragmentation of the beam are evaluated. The GERM code is a computationally efficient Monte-Carlo heavy-ion-beam model. It includes accurate models of LET, range, residual energy, and straggling, and the quantum multiple scattering fragmentation (QMSGRG) nuclear database.

Cucinotta, Francis A.↗

Cosmic heavy ion tracks in mesoscopic biological test objects

Since more than 20 years ago, when the National Academy of Sciences and the National Research Council of the U.S.A. released their report on 'HZE particle effects in manned spaced flight', it has been emphasized how difficult - if not even impossible - it is to assess their radiobiological impact on man from conventional studies where biological test organisms are stochastically exposed to 'large' fluences of heavy ions. An alternative, competing approach had been realized in the BIOSTACK experiments, where the effects of single cosmic as well as accelerator - heavy ions on individual biological test organisms could be investigated. Although presented from the beginning as the preferable approach for terrestrial investigations with accelerator heavy ions too ('The BIOSTACK as an approach to high LET radiation research'), only recently this insight is gaining more widespread recognition. In space flight experiments, additional constraints imposed by the infrastructure of the vehicle or satellite further impede such investigations. Restrictions concern the physical detector systems needed for the registration of the cosmic heavy ions' trajectories as well as the biological systems eligible as test organisms. Such optimized procedures and techniques were developed for the investigations on chromosome aberrations induced by cosmic heavy ions in cells of the stem meristem of lettuce seeds (Lactuca sativa) and for the investigation of the radiobiological response of Wolffia arriza, which is the smallest flowering (water) plant. The biological effects were studied by the coworkers of the Russian Institute of Biomedical Problems (IBMP) which in cooperation with the European Space Agency ESA organized the exposure in the Biosatellites of the Cosmos series. Since biological investigations and physical measurements of particle tracks had to be performed in laboratories widely separated, the preferred fixed contact between biological test objects and the particle detectors until the geometrical correlation between tracks and organisms has been established could not be maintained. This gave rise to half a dozen of coordinate systems for different measurements which finally had to be related to a single stack reference system.

Facius, R.↗

Potential health effects of space radiation

Crewmembers on missions to the Moon or Mars will be exposed to radiation belts, galactic cosmic rays, and possibly solar particle events. The potential health hazards due to these space radiations must be considered carefully to ensure the success of space exploration. Because there is no human radioepidemiological data for acute and late effects of high-LET (Linear-Energy-Transfer) radiation, the biological risks of energetic charged particles have to be estimated from experimental results on animals and cultured cells. Experimental data obtained to date indicate that charged particle radiation can be much more effective than photons in causing chromosome aberrations, cell killing, mutation, and tumor induction. The relative biological effectiveness (RBE) varies with biological endpoints and depends on the LET of heavy ions. Most lesions induced by low-LET radiation can be repaired in mammalian cells. Energetic heavy ions, however, can produce large complex DNA damages, which may lead to large deletions and are irreparable. For high-LET radiation, therefore, there are less or no dose rate effects. Physical shielding may not be effective in minimizing the biological effects on energetic heavy ions, since fragments of the primary particles can be effective in causing biological effects. At present the uncertainty of biological effects of heavy particles is still very large. With further understanding of the biological effects of space radiation, the career doses can be kept at acceptable levels so that the space radiation environment need not be a barrier to the exploitation of the promise of space.

Yang, Chui-Hsu↗

Shielded Heavy-Ion Environment Linear Detector (SHIELD): an experiment for the Radiation and Technology Demonstration (RTD) Mission

Radiological assessment of the many cosmic ion species of widely distributed energies requires the use of theoretical transport models to accurately describe diverse physical processes related to nuclear reactions in spacecraft structures, planetary atmospheres and surfaces, and tissues. Heavy-ion transport models that were designed to characterize shielded radiation fields have been validated through comparison with data from thick-target irradiation experiments at particle accelerators. With the RTD Mission comes a unique opportunity to validate existing radiation transport models and guide the development of tools for shield design. For the first time, transport properties will be measured in free-space to characterize the shielding effectiveness of materials that are likely to be aboard interplanetary space missions. Target materials composed of aluminum, advanced composite spacecraft structure and other shielding materials, helium (a propellant) and tissue equivalent matrices will be evaluated. Large solid state detectors will provide kinetic energy and charge identification for incident heavy-ions and for secondary ions created in the target material. Transport calculations using the HZETRN model suggest that 8 g cm -2 thick targets would be adequate to evaluate the shielding effectiveness during solar minimum activity conditions for a period of 30 days or more.

NASA Center LaRC↗

Performance study of galactic cosmic ray shield materials

The space program is faced with two difficult radiation protection issues for future long-term operations. First, retrofit of shield material or conservatism in shield design is prohibitively expensive and often impossible. Second, shielding from the cosmic heavy ions is faced with limited knowledge on the physical properties and biological responses of these radiations. The current status of space shielding technology and its impact on radiation health is discussed herein in terms of conventional protection practice and a test biological response model. The impact of biological response on the selection of optimum materials for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although the systematics of nuclear cross sections are able to demonstrate the relation of exposure risk to shield-material composition, the current uncertainty in-nuclear cross sections will not allow an accurate evaluation of risk reduction. This paper presents a theoretical study of risk-related factors and a pilot experiment to study the effectiveness of choice of shield materials to reduce the risk in space operations.

Kim, Myung-Hee Y.↗

An improved Green's function for ion beam transport

Ion beam transport theory allows testing of material transmission properties in the laboratory environment generated by particle accelerators. This is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are the main emphasis of the present work. In consequence, an analytic solution of the linear Boltzmann equation is pursued in the form of a Green's function allowing flexibility in application to a broad range of boundary value problems. It has been established that simple solutions can be found for high charge and energy (HZE) ions by ignoring nuclear energy downshifts and dispersion. Such solutions were found to be supported by experimental evidence with HZE ion beams when multiple scattering was added. Lacking from the prior solutions were range and energy straggling and energy downshift with dispersion associated with nuclear events. Recently, we have found global solutions including these effects providing a broader class of HZE ion solutions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Center LaRC↗

Background of the completed research; relevances to solar physics

Research activities reported consider the atomic structures of highly stripped heavy ions and their modes of formation and destruction in collisions. The lifetime of the metastable 2 3p1 state of the two electron ion F-7(+) was determined by measuring the radiative decay of an excited helium-like fluorine beam, Metastable state quenching measurements were performed on a helium-like ion to obtain the 1 1S0 to 2 3p2 transition probability. Exponential exchange state dependence of X-ray production cross sections was studied in heavy target atoms during collisions with light charged particles.

Sellin, I. A.↗

Theoretical model of HZE particle fragmentation by hydrogen targets

The fragmenting of high energy, heavy ions (HZE particles) by hydrogen targets is an important, physical process in several areas of space radiation research. In this work quantum mechanical optical model methods for estimating cross sections for HZE particle fragmentation by hydrogen targets are presented. The cross sections are calculated using a modified abrasion-ablation collision formalism adapted from a nucleus-nucleus collision model. Elemental and isotopic production cross sections are estimated and compared with reported measurements for the breakup of neon, sulphur, and iron, nuclei at incident energies between 400 and 910 Mev/nucleon. Good agreement between theory and experiment is obtained.

Townsend, L.W.↗

Issues In Space Radiation Protection: Galactic Cosmic Rays

When shielding from cosmic heavy ions, one is faced with limited knowledge about the physical properties and biological responses of these radiations. Herein, the current health is discussed in terms of conventional protection practice and a test biological response model. The impact of biological response on optimum materials selection for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although liquid hydrogen is an optimum shield material, evaluation of the effectiveness of polymeric structural materials must await improvement in our knowledge of both the biological response and the nuclear processes.

Wilson, J. W.↗

Issues in Space Radiation Protection: Galactic Cosmic Rays

With shielding from cosmic heavy ions, one is faced with limited knowledge about the physical properties and biological responses of these radiations. Herein, the current status of space shielding technology and its impact on radiation health is discussed in terms of conventional protection practice and a test biological response model. The impact of biological response on optimum materials selection for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although liquid hydrogen gas is an optimum shield material, evaluation of the effectiveness of polymeric structural materials must await improvement in our knowledge of both the biological response and the nuclear processes.

Wilson, J. W.↗

Development of a GCR Event-based Risk Model

A goal at NASA is to develop event-based systems biology models of space radiation risks that will replace the current dose-based empirical models. Complex and varied biochemical signaling processes transmit the initial DNA and oxidative damage from space radiation into cellular and tissue responses. Mis-repaired damage or aberrant signals can lead to genomic instability, persistent oxidative stress or inflammation, which are causative of cancer and CNS risks. Protective signaling through adaptive responses or cell repopulation is also possible. We are developing a computational simulation approach to galactic cosmic ray (GCR) effects that is based on biological events rather than average quantities such as dose, fluence, or dose equivalent. The goal of the GCR Event-based Risk Model (GERMcode) is to provide a simulation tool to describe and integrate physical and biological events into stochastic models of space radiation risks. We used the quantum multiple scattering model of heavy ion fragmentation (QMSFRG) and well known energy loss processes to develop a stochastic Monte-Carlo based model of GCR transport in spacecraft shielding and tissue. We validated the accuracy of the model by comparing to physical data from the NASA Space Radiation Laboratory (NSRL). Our simulation approach allows us to time-tag each GCR proton or heavy ion interaction in tissue including correlated secondary ions often of high multiplicity. Conventional space radiation risk assessment employs average quantities, and assumes linearity and additivity of responses over the complete range of GCR charge and energies. To investigate possible deviations from these assumptions, we studied several biological response pathway models of varying induction and relaxation times including the ATM, TGF -Smad, and WNT signaling pathways. We then considered small volumes of interacting cells and the time-dependent biophysical events that the GCR would produce within these tissue volumes to estimate how GCR event rates mapped to biological signaling induction and relaxation times. We considered several hypotheses related to signaling and cancer risk, and then performed simulations for conditions where aberrant or adaptive signaling would occur on long-duration space mission. Our results do not support the conventional assumptions of dose, linearity and additivity. A discussion on how event-based systems biology models, which focus on biological signaling as the mechanism to propagate damage or adaptation, can be further developed for cancer and CNS space radiation risk projections is given.

Cucinotta, Francis A.↗

Space Environment (Natural and Induced)

Considerable effort and improvement have been made in the study of ionizing radiation exposure occurring in various regions of space. Satellites and spacecrafts equipped with innovative instruments are continually refining particle data and providing more accurate information on the ionizing radiation environment. The major problem in accurate spectral definition of ionizing radiation appears to be the detailed energy spectra, especially at high energies, which is important parameter for accurate radiation risk assessment. Magnitude of risks posed by exposure to radiation in future space missions is subject to the accuracies of predictive forecast of event size of SPE, GCR environment, geomagnetic fields, and atmospheric radiation environment. Although heavy ion fragmentations and interactions are adequately resolved through laboratory study and model development, improvements in fragmentation cross sections for the light nuclei produced from HZE nuclei and their laboratory validation are still required to achieve the principal goal of planetary GCR simulation at a critical exposure site. More accurate prediction procedure for ionizing radiation environment can be made with a better understanding of the solar and space physics, fulfillment of required measurements for nuclear/atomic processes, and their validation and verification with spaceflights and heavy ion accelerators experiments. It is certainly true that the continued advancements in solar and space physics combining with physical measurements will strengthen the confidence of future manned exploration of solar system. Advancements in radiobiology will surely give the meaningful radiation hazard assessments for short and long term effects, by which appropriate and effective mitigation measures can be placed to ensure that humans safely live and work in the space, anywhere, anytime.

Kim, Myung-Hee Y.↗