Possible effects of protracted exposure on the additivity of risks from space radiations.

Conventional radiation risk assessments are presently based on the additivity assumption. This assumption states that risks from individual components of a complex radiation field involving many different types of radiation can be added to yield the total risk of the complex radiation field. If the assumption is not correct, the summations and integrations performed to obtain the presently quoted risk estimates are not appropriate. This problem is particularly important in the area of space radiation risk evaluation because of the many different types of high- and low-LET radiation present in the galactic cosmic ray environment. For both low- and high-LET radiations at low enough dose rates, the present convention is that the addivity assumption holds. Mathematically, the total risk, Rtot is assumed to be Rtot = summation (i) Ri where the summation runs over the different types of radiation present. If the total dose (or fluence) from each component is such that the interaction between biological lesions caused by separate single track traversals is negligible within a given cell, it is presently considered to be reasonable to accept the additivity assumption. However, when the exposure is protracted over many cell doubling times (as will be the case for extended missions to the moon or Mars), the possibility exists that radiation effects that depend on multiple cellular events over a long time period, such as is probably the case in radiation-induced carcinogenesis, may not be additive in the above sense and the exposure interval may have to be included in the evaluation procedure. It is shown, however, that "inverse" dose-rate effects are not expected from intermediate LET radiations arising from the galactic cosmic ray environment due to the "sensitive-window-in-the-cell-cycle" hypothesis.     

Galactic cosmic rays and cell-hit frequencies outside the magnetosphere.

An evaluation of the exposure of space travelers to galactic cosmic radiation outside the earth's magnetosphere is made by calculating fluences of high-energy primary and secondary particles with various charges traversing a sphere of area 100 microns2. Calculations relating to two shielding configurations are presented: the center of a spherical aluminum shell of thickness 1 g/cm2, and the center of a 4 g/cm2 thick aluminum spherical shell within which there is a 30 g/cm2 diameter spherical water phantom with the point of interest 5 g/cm2 from the surface. The area of 100 microns2 was chosen to simulate the nucleus of a cell in the body. The frequencies as a function of charge component in both shielding configurations reflects the odd-even disparity of the incident particle abundances. For a three-year mission, 33% of the cells in the more heavily shielded configuration would be hit by at least one particle with Z greater than 10. Six percent would be hit by at least two such particles. This emphasizes the importance of studying single high-Z particle effects both on cells which might be "at risk" for cancer induction and on critical neural cells or networks which might be vulnerable to inactivation by heavy charged particle tracks. Synergistic effects with the more numerous high-energy protons and helium ions cannot be ruled out. In terms of more conventional radiation risk assessment, the dose equivalent decreased by a factor of 2.85 from free space to that in the more heavily shielded configuration. Roughly half of this was due to the decrease in energy deposition (absorbed dose) and half to the decrease in biological effectiveness (quality factor).     

Assessment and requirements of nuclear reaction databases for GCR transport in the atmosphere and structures

The transport properties of galactic cosmic rays (GCR) in the atmosphere, material structures, and human body (self-shielding) are of interest in risk assessment for supersonic and subsonic aircraft and for space travel in low-Earth orbit and on interplanetary missions. Nuclear reactions, such as knockout and fragmentation, present large modifications of particle type and energies of the galactic cosmic rays in penetrating materials. We make an assessment of the current nuclear reaction models and improvements in these model for developing required transport code data bases. A new fragmentation data base (QMSFRG) based on microscopic models is compared to the NUCFRG2 model and implications for shield assessment made using the HZETRN radiation transport code. For deep penetration problems, the build-up of light particles, such as nucleons, light clusters and mesons from nuclear reactions in conjunction with the absorption of the heavy ions, leads to the dominance of the charge Z = 0, 1, and 2 hadrons in the exposures at large penetration depths. Light particles are produced through nuclear or cluster knockout and in evaporation events with characteristically distinct spectra which play unique roles in the build-up of secondary radiation's in shielding. We describe models of light particle production in nucleon and heavy ion induced reactions and make an assessment of the importance of light particle multiplicity and spectral parameters in these exposures.     

Importance of dose-rate and cell proliferation in the evaluation of biological experimental results.

The nuclei of cells within the bodies of astronauts traveling on extended missions outside the geomagnetosphere will experience single traversals of particles with high LET (e.g., one iron ion per one hundred years, on average) superimposed on a background of tracks with low LET (approximately one proton every two to three days, and one helium ion per month). In addition, some cell populations within the body will be proliferating, thus possibly providing increasing numbers of cells with "initiated" targets for subsequent radiation hits. These temporal characteristics are not generally reproduced in laboratory experimental protocols. Implications of the differences in the temporal patterns of radiation delivery between conventionally designed radiation biology experiments and the pattern to be experienced in space are examined and the importance of dose-rate and cell proliferation are pointed out in the context of radiation risk assessment on long missions in space.     

A comparison of total reaction cross section models used in particle and heavy ion transport codes

Understanding the interactions and propagations of high energy protons and heavy ions are essential when trying to estimate the biological effects of Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE) on personnel in space. To be able to calculate the shielding properties of different materials and radiation risks, particle and heavy ion transport codes are needed. In all particle and heavy ion transport codes, the probability function that a projectile particle will collide within a certain distance x in the matter depends on the total reaction cross sections, and the calculated partial fragmentation cross sections scale with the total reaction cross sections. It is therefore crucial that accurate total reaction cross section models are used in the transport calculations. In this paper, different models for calculating nucleon–nucleus and nucleus–nucleus total reaction cross sections are compared with each other and with measurements. The uncertainties in the calculations with the different models are discussed, as well as their overall performances with respect to the available experimental data. Finally, a new compilation of experimental data is briefly presented.     

An assessment of galactic cosmic radiation quality considering heavy ion track structures within the cellular environment.

Beyond the magnetic influence of the Earth, the flux of galactic cosmic radiation (GCR) represents a radiological concern for long-term manned space missions. Current concepts of radiation quality and equivalent dose are inadequate for accurately specifying the relative biological "efficiency" of low doses of such heavily ionising radiations, based as they are on the single parameter of Linear Energy Transfer (LET). Such methods take no account of the mechanisms, nor of the highly inhomogeneous spatial structure, of energy deposition in radiation tracks. DNA damage in the cell nucleus, which ultimately leads to the death or transformation of the cell, is usually initiated by electrons liberated from surrounding molecules by the incident projectile ion. The characteristics of these emitted "delta-rays", dependent primarily upon the charge and velocity of the ion, are considered in relation to an idealised representation of the cellular environment. Theoretically calculated delta-ray energy spectra are multiplied by a series of weighting algorithms designed to represent the potential for DNA insult in this environment, both in terms of the quantity and quality of damage. By evaluating the resulting curves, and taking into account the energy spectra of heavy ions in space, a relative measure of the biological relevance of the most abundant GCR species is obtained, behind several shielding configurations. It is hoped that this method of assessing the radiation quality of galactic cosmic rays will be of value when considering the safety of long-term manned space missions.     

Nuclear fragmentation database for GCR transport code development

A critical need for NASA is the ability to accurately model the transport of heavy ions in the Galactic Cosmic Rays (GCR) through matter, including spacecraft walls, equipment racks, etc. Nuclear interactions are of great importance in the GCR transport problem, as they can cause fragmentation of the incoming ion into lighter ions. Since the radiation dose delivered by a particle is proportional to the square of (charge/velocity), fragmentation reduces the dose delivered by incident ions. The other mechanism by which dose can be reduced is ionization energy loss, which can lead to some particles stopping in the shielding. This is the conventional notion of shielding, but it is not applicable to human spaceflight since the particles in the GCR tend to be too energetic to be stopped in the relatively thin shielding that is possible within payload mass constraints. Our group has measured a large number of fragmentation cross sections, intended to be used as input to, or for validation of, NASA’s radiation transport models. A database containing over 200 charge-changing cross sections and over 2000 fragment production cross sections has been compiled. In this report, we examine in detail the contrast between fragment measurements at large acceptance and small acceptance. We use output from the PHITS Monte Carlo code to test our assumptions using as an example ⁴⁰Ar data (and simulated data) at a beam energy of 650 MeV/nucleon. We also present preliminary analysis in which isotopic resolution was attained for beryllium fragments produced by beams of ¹⁰B and ¹¹B. Future work on the experimental data set will focus on extracting and interpreting production cross sections for light fragments.     

Radiation issues for piloted Mars mission.

Man is now entering an era of colonizing the moon and exploration of Mars. The crewmembers of a piloted mission to Mars will be exposed to inner belt trapped protons, the outer trapped electrons, and the galactic cosmic radiation. In addition there is always the added risk of acute exposure to a solar particle event. Current radiation risk is estimated using the idea of absorbed dose and ICRP-26, LET-dependent quality factors. In a spacecraft with aluminum walls (2 g cm-2) at solar minimum the calculated dose equivalent is 0.73 Sv for a 406-day mission. Based on the current thinking this leads to an excess cancer mortality in a 35 year male of about 1%. About 75% of the dose equivalent is contributed by HZE particles and target fragments with average quality factors of 10.3 and 20, respectively. The entire concept of absorbed dose, quality factor, and dose equivalent as applied to such missions needs to be reexamined, in light of the fact that less than 50% of the nuclei in the body of the astronaut would have been traversed by a single GCR nuclei in the 406-day mission. Clearly, more biologically relevant information about the effects of heavy ions and target fragments is needed and fluence based risk estimation strategy developed for such long term stays in space.     

Nuclear model calculations and their role in space radiation research.

Proper assessments of spacecraft shielding requirements and concomitant estimates of risk to spacecraft crews from energetic space radiation requires accurate, quantitative methods of characterizing the compositional changes in these radiation fields as they pass through thick absorbers. These quantitative methods are also needed for characterizing accelerator beams used in space radiobiology studies. Because of the impracticality/impossibility of measuring these altered radiation fields inside critical internal body organs of biological test specimens and humans, computational methods rather than direct measurements must be used. Since composition changes in the fields arise from nuclear interaction processes (elastic, inelastic and breakup), knowledge of the appropriate cross sections and spectra must be available. Experiments alone cannot provide the necessary cross section and secondary particle (neutron and charged particle) spectral data because of the large number of nuclear species and wide range of energies involved in space radiation research. Hence, nuclear models are needed. In this paper current methods of predicting total and absorption cross sections and secondary particle (neutrons and ions) yields and spectra for space radiation protection analyses are reviewed. Model shortcomings are discussed and future needs presented.     

K-ionization and biological effect.

Experimental inactivation cross sections are compared to vacancy production in inner shell (K-shell) of so-called strategic C, N, O atoms of the DNA: in a trial calculation, atoms on the DNA backbone or just contiguous to it are considered as strategic. Various processes are considered: ionization and electron capture by the primary particle, ionization by secondary electrons. The last phenomenon is shown to be important for highly charged and medium velocity ions. A strong similarity is observed between variations versus LET of inactivation and K-vacancy cross sections, especially with regards to LET values for which they maximize: for K-ionization these maxima occur when the ion impact velocity roughly matches the K electron velocity. It is shown that the "K-hypothesis" allows a quantitative fit of experimental inactivation cross sections if a 4% mean lethal efficiency is attributed to ion-induced K-vacancies in strategic C, N, O atoms.     

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 report 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.     

Cellular and subcellular effect of heavy ions: a comparison of the induction of strand breaks and chromosomal aberration with the incidence of inactivation and mutation.

Radiobiological effects of heavy charged particles are compared for a large variety of ions from Helium to Uranium and energies between 1 and 1000 MeV/u which correspond to LET values between 10 and 16000 keV/micrometers. The different cross section for the induction of strand breaks and chromosomal aberrations as well as for inactivation and mutation induction exhibit striking similarities when compared as function of the linear energy transfer (LET). At LET values below 100 keV/micrometers all data points of one specific effect form one single curve as a function of LET, independent of the atomic number of the ion. In this LET range, the biological effects are independ from the particle energy or track structure and depend only on the energy transfer. Therefore, LET is a good parameter in this regime. For LET values greater than 100 keV/micrometers, the curves for the different ions separate from the common curve in order of increasing atomic numbers. In this regime LET is no longer a good parameter and the physical parameters of the formation of particle tracks are important. The similarity of the sigma-LET curves for different endpoints indicates that the 'hook-structure' is produced by physical and chemical effects which occur before the biologically relevant lesions are formed. However, from the existing data of biological effects, it can be concluded that the efficiencies for cell killing are always smaller than those extrapolated from X-ray data on the basis of the energy deposition only. Therefore, cells which are directly hit by an HZE particle are not killed and undergo a finite risk of mutation and transformation.     

Radiation effects on late cytopathological parameters in the murine lens relative to particle fluence.

Lenses of mice irradiated with 250 MeV protons, 670 MeV/amu 20Ne, 600 MeV/amu 56Fe, 600 MeV/amu 93Nb and 593 MeV/amu 139La ions were evaluated by analyzing cytopathological indicators which have been implicated in the cataractogenic process. The LETs ranged from 0.40 keV/micrometer to 953 keV/micrometer and fluences from 1.31 10(3)/mm2 to 4.99 x 10(7)/mm2. 60Co gamma-rays were used as the reference radiation. The doses ranged from 10 to 40 cGy. The lenses were assessed 64 weeks post irradiation in order to observe the late effects of LET and dose on the target cell population of the lens epithelium. Our study shows that growth dependent pathological changes occur at the cellular level as a function of dose and LET. The shapes of the RBE-LET and RBE-dose curves are consistent with previous work on eye and other biological systems done in both our laboratory and others. The RBEmax's were estimated, for the most radiation cataract related cytological changes, MN frequency and MR disorganization, by calculating the ratio of the initial slopes of dose effect curve for various heavy ions to that of 60Co gamma-ray. For each ion studied, the RBEmax derived from micronucleus (MN) frequency is similar to that derived from meridional row (MR) disorganization, suggesting that heavy ions are equally efficient at producing each type of damage. Furthermore, on a per particle basis (particle/cell nucleus), both MN frequency and MR disorganization are LET dependent indicating that these classic precataractogenic indicators are multi-gene effects. Poisson probability analysis of the particle number traversing cell nuclei (average area = 24 micrometers2) suggested that single nuclear traversals determine these changes. By virtue of their precataractogenic nature the data on these endpoints intimate that radiation cataract may also be the consequence of single hits. In any case, these observations are consistent with the current theory of the mechanism of radiation cataractogenesis, which proposes that genomic damage to the epithelial cells surviving the exposure is responsible for opacification.     

Approaches to radiation guidelines for space travel.

There are obvious risks in space travel that have loomed larger than any risk from radiation. Nevertheless, NASA has maintained a radiation program that has involved maintenance of records of radiation exposure, and planning so that the astronauts' exposures are kept as low as possible, and not just within the current guidelines. These guidelines are being reexamined currently by NCRP Committee 75 because new information is available, for example, risk estimates for radiation-induced cancer and about the effects of HZE particles. Furthermore, no estimates of risk or recommendations were made for women in 1970 and must now be considered. The current career limit is 400 rem to the blood forming organs. The appropriateness of this limit and its basis are being examined as well as the limits for specific organs. There is now considerably more information about age-dependency for radiation effects and this will be taken into account. In 1973 a committee of the National Research Council made a separate study of HZE particle effects and it was concluded that the attendant risks did not pose a hazard for low inclination near-earth orbit missions. Since that time work has been carried out on the so-called microlesions caused by HZE particles and on the relative carcinogenic effect of heavy ions, including iron. A remaining question is whether the fluence of HZE particles could reach levels of concern in missions under consideration. Finally, it is the intention of the committee to indicate clearly the areas requiring further research.     

Transport of light ions in matter

A recent set of light ion experiments are analyzed using the Green's function method of solving the Boltzmann equation for ions of high charge and energy (the GRNTRN transport code) and the NUCFRG2 fragmentation database generator code. Although the NUCFRG2 code reasonably represents the fragmentation of heavy ions, the effects of light ion fragmentation requires a more detailed nuclear model including shell structure and short range correlations appearing as tightly bound clusters in the light ion nucleus. The most recent NUCFRG2 code is augmented with a quasielastic alpha knockout model and semiempirical adjustments (up to 30 percent in charge removal) in the fragmentation process allowing reasonable agreement with the experiments to be obtained. A final resolution of the appropriate cross sections must await the full development of a coupled channel reaction model in which shell structure and clustering can be accurately evaluated.     

Liquid drop model considerations in HZE particle fragmentation by hydrogen

The fragmenting of high energy, heavy ions by hydrogen targets is an important physical process in several areas of space radiation protection research. Quantum mechanical, optical model methods for calculating cross sections for particle fragmentation by hydrogen have been developed from a modified abrasion-ablation collision formalism. The abrasion stage is treated as a knockout process which leaves the residual prefragment in an excited state. In the ablation stage the prefragment deexcites to produce the final fragment. The prefragment excitation energies are estimated from a combination of liquid drop model considerations and frictional-spectator interaction processes. Estimates of elemental and isotopic production cross sections are in good agreement with published cross section measurements.     

Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland.

Neoplasia in the rodent Harderian gland has been used to determine the carcinogenic potential of irradiation by HZE particles. Ions from protons to lanthanum at energies up to 670 MeV/a have been used to irradiate mice, and prevalence of Harderian gland tumors has been measured 16 months after irradiation. The RBE for tumor induction has been expressed as the RBEmax, which is the ratio of the initial slopes of the dose vs prevalence curve. The RBEmax has been found to be approximately 30 for ions with LET values in excess of 100 keV/micrometer. Analysis on the basis of fluence as a substitute for dose has shown that on a per particle basis all of the ions with LET values in excess of 100 keV/micrometer have equal effectiveness. An analysis of the probabilities of ion traversals of the nucleus has shown that for these high stopping powers that a single hit is effective in producing neoplastic transformation.     

Uncertainties in estimates of the risks of late effects from space radiation.

Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Using the linear-additivity model for radiation risks, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain an estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including a deep space outpost and Mars missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative metrics, e.g., the number of days in space without exceeding a given risk level within well-defined confidence limits.     

Fluence-related risk coefficients using the Harderian gland data as an example.

The risk of radiation-induced cancer to space travelers outside the earth's magnetosphere will be of concern on missions to the Moon and beyond to Mars. High energy galactic cosmic rays with high charge (HZE particles) will penetrate the spacecraft and the bodies of the astronauts, sometimes fragmenting into nuclear secondary species of lower charge but always ionizing densely, thus causing cellular damage which may lead to malignant transformation. To quantitate this risk, the concept of dose equivalent (in which a quality factor Q as a function of LET is assumed) may not be adequate, since different particles of the same LET may have different efficiencies for tumor induction. Also, RBE values on which quality factors are based depend on response to low-LET radiation at low doses, a very difficult region for which to obtain reliable experimental data. Thus, we introduce a new concept, a fluence-related risk coefficient (F), which is the risk of a cancer per unit particle fluence and which we call the risk cross section. The total risk is the sum of the risk from each particle type: sigma i integral Fi(Li) phi i(Li) dLi, where Li is the LET and phi i(Li) is the fluence-LET spectrum of the ith particle type. As an example, tumor prevalence data in mice are used to estimate the probability of mouse Harderian gland tumor induction per year on an extra-magnetospheric mission inside an idealized shielding configuration of a spherical aluminum shell 1 g/cm2 thick. The combined shielding code BRYNTRN/GCR is used to generate the LET spectra at the center of the sphere. Results indicate a yearly prevalence at solar minimum conditions of 0.06, with 60% of this arising from charge components with Z between 10 and 28, and two-thirds of the contribution arising from LET components between 10 and 200 keV/micrometers.