Unique radiobiological aspects of high-LET radiation.

Since the beg inning of manned space flight the potentially unique radiobiological properties of the heavy ions of the cosmic radiation had been, apart from possible interactions of radiation effects with biological effects of weightlessness, of major concern with respect to the assessment of radiation hazards in manned space flight. Radiobiological findings obtained from space flight experiments and ground based experiments with densely ionizing radiation are discussed, which suggest qualitative differences between the radiobiological mechanisms of sparsely ionizing and densely ionizing radiation. These findings comprise the observation of a long lateral range of radiobiological effectiveness around tracks of single heavy ions, the observation of micro lesions induced in biological targets by the penetration of heavy ions, the nonadditivity of radiobiological effects from sparsely and densely ionizing radiation, the different kinetics for the expression of late effects induced by sparsely or densely ionizing radiation, and the observation of a reversed dose rate effect for early and late effects induced by densely ionizing radiation. These findings bear on the radiation protection standards to be installed for a general public in manned space flight and on the design of experiments, which intend to contribute to their specification.     

Recent results of comparative radiobiological experiments with short and long term expositions of arabidopsis seed embryos

Comparison of experimental data obtained from short (SDEF) and long duration exposure flights (LDEF) recently led to results, which will contribute for the estimation of genetic risk for long and/or repeated stay of man in space. Under orbital conditions biological stress and damage are induced in test subjects by cosmic radiation, especially the high energetic, densely ionizing component of heavy ions. Plant seeds were successful model systems for a biotest in studying the physiological damages and mutagenic effects caused by ionizing radiation in particular stem cells. In this article we present an overview of our space experiments with Arabidopis thaliana seeds. We present first results of investigations on certain damage endpoints (seed germination, plant survival, mutation frequencies), caused by cosmic ionizing radiation in dry dormant plant seeds of Arabidopsis thaliana after different short term (e.g. IML-1 and D-2) and long term (e.g. EURECA and LDEF-1) space exposures. Total dose effects of heavy ions and the other components of the mixed radiation field on damage endpoints and survival after space exposure and gamma-ray preirradiation were obtained. A new method of total dose spectrometry by neutron activation has been applied.     

Radiation protection problems for the space station and approaches to their mitigation.

With the advent of a permanent manned space station the longstanding problems of radiation protection in manned spaceflight have acquired an immediacy. This paper endeavors to emphasize the gaps of our knowledge which must be closed for effective radiation protection. The information that is required includes the accurate determination of the exposure inside the space station to the various components of tile ionizing radiation, the evaluation of the biological importance of the different radiation qualities and the depth dose distribution of the less penetrating component. There is also the possibility of an interaction with weightlessness. It is necessary to establish adequate radiation protection standards and a system of dosimetric surveillance. There is a need for studies of possible methods of hardening selective shielding of the space station. Spaceflight experiments, which might contribute to the solution of some of these problems are discussed.     

R3D-B2 – Measurement of ionizing and solar radiation in open space in the BIOPAN 5 facility outside the FOTON M2 satellite

Solar and space radiation have been monitored using the R3D-B2 radiation risks radiometer-dosimeter on board a recent space flight on the Russian satellite Foton M2 within the ESA Biopan 5 facility mounted on the outside of the satellite exposed to space conditions. The solar radiation has been assayed in four wavelength bands (UV-C, 170–280 nm, UV-B, 280–315 nm), UV-A (315–400 nm) and PAR (photosynthetic active radiation, 400–700 nm). The data show an increasing tumbling rotation of the satellite during the mission. The photodiodes do not show a cosine response to the incident light which has been corrected. After calibration of the signals using the extraterrestrial spectrum, doses have been calculated for each orbit, for each day and for the total mission as basic data for the biological material which has been exposed in parallel in the Biopan facility. Cosmic ionizing radiation has been monitored and separated in 256 deposited energy spectra, which were further used for determination of the absorbed dose rate and flux. Basic data tables were prepared to be used by other Biopan 5 experiments. The paper summarizes the results for the Earth radiation environment at the altitude (262–304 km) of the Foton M2 spacecraft. Comparisons with the predictions of NASA Earth radiation environment experimental models AE-8 and AP-8, and the PSB97 model are also presented, which calculate the fluxes of ionizing radiation from a simulation. AP-8 is a model for trapped radiation.     

二次包封CMOS器件电子辐照实验研究

对CMOS器件54HCT00进行了复合材料的二次包封，研制了试验电路板，在器件加电工作下进行电子辐照试验的动态测试．结果表明，二次封装的器件抗总剂量的能力提高了1—2个数量级，得到了预期的数据和结果．这些工作为商用器件的空间开拓使用提供了很好的途径．     

Simultaneous measurement of multiple radiation-induced protein expression profiles using the Luminex(TM) system.

Space flight results in the exposure of astronauts to a mixed field of radiation composed of energetic particles of varying energies, and biological indicators of space radiation exposure provides a better understanding of the associated long-term health risks. Current methods of biodosimetry have employed the use of cytogenetic analysis for biodosimetry, and more recently the advent of technological progression has led to advanced research in the use of genomic and proteomic expression profiling to simultaneously assess biomarkers of radiation exposure. We describe here the technical advantages of the Luminex(TM) 100 system relative to traditional methods and its potential as a tool to simultaneously profile multiple proteins induced by ionizing radiation. The development of such a bioassay would provide more relevant post-translational dynamics of stress response and will impart important implications in the advancement of space and other radiation contact monitoring.     

Estimation of a cosmonaut's radiation hazard during long-term space missions on the basis of a generalized dosimetric function.

This paper presents a new concept of radiation hazard assessment for spacecraft crew members during long term space missions on the basis of a generalized dosimetric function. This new dosimetric function enables a complicated nature of space radiation exposure to be reduced to the conditions of a standard irradiation. It can be obtained on the basis of mean-tissue equivalent dose values calculated for each space radiation source and transmission coefficients describing the influence of the complex spatial and temporal distribution of the absorbed dose in the cosmonaut's body on the radiobiological effects. The combination of cosmic ionizing radiation with other non-radiation nature factors in flight can also be accounted for. In terms of the generalized dose, it is possible to assess the nature and extent of lowering a crew working capacity, as well as radiation risk, both during a flight and post flight period.     

Ground-based research with heavy ions for space radiation protection.

Human exposure to ionizing radiation is one of the acknowledged potential showstoppers for long duration manned interplanetary missions. Human exploratory missions cannot be safely performed without a substantial reduction of the uncertainties associated with different space radiation health risks, and the development of effective countermeasures. Most of our knowledge of the biological effects of heavy charged particles comes from accelerator-based experiments. During the 35th COSPAR meeting, recent ground-based experiments with high-energy iron ions were discussed, and these results are briefly summarised in this paper. High quality accelerator-based research with heavy ions will continue to be the main source of knowledge of space radiation health effects and will lead to reductions of the uncertainties in predictions of human health risks. Efforts in materials science, nutrition and pharmaceutical sciences and their rigorous evaluation with biological model systems in ground-based accelerator experiments will lead to the development of safe and effective countermeasures to permit human exploration of the Solar System.     

A model of the effects of heavy ion radiation on human tissue

In heavy ion radiotherapy and space travel humans are exposed to energetic heavy ions (C, Si, Fe and others). This type of irradiation often produces more severe biological effects per unit dose than more common X-rays. A new Monte Carlo model generates a physical space with the complex geometry of human tissue or a cell culture based model of tissue, which is affected by the passage of ionizing radiation. For irradiation, the model relies on a physical code for the ion track structure; for tissues, cellular maps are derived from two- or three-dimensional confocal microscopy images using image segmentation algorithm, which defines cells as pixilated volumes. The model is used to study tissue-specific statistics of direct ion hits and the remote ion action on cells. As an application of the technique, we considered the spatial pattern of apoptotic cells after heavy ion irradiation. The pattern of apoptosis is modeled as a stochastic process, which is defined by the action cross section taken from available experimental data. To characterize the degree of apoptosis, an autocorrelation function that describes the spatial correlation of apoptotic cells is introduced. The values of the autocorrelation function demonstrate the effect of the directionality of the radiation track on the spatial arrangements of inactivated cells in tissue. This effect is intrinsic only to high linear-energy-transfer radiation.     

Track structure and DNA damage.

Heavy particles like protons or heavier ions are different in their biological efficiency when compared to sparsely ionizing radiation. These differences have been attributed to the different pattern of energy deposition in the track of the particles. In radiobiological models two different approaches are used for the characterization of the radiation quality: the continuous dose distribution of the various track structure models and the separation in small compartments inside the track which are used in microdosimetry. In a recent Monte Carlo calculation using the binary encounter approximation as input for the electron emission process, the radial distribution of the dose is calculated for heavy ions. The result of this calculation is compared to other models and used for a qualitative interpretation of the induction of DNA damage by particles.     

Cosmic ionizing radiation effects in plant seeds after short and long duration exposure flights.

Recently, comparison of biophysical data obtained from orbital flights of short and long duration led to results which will be significant for long and/or repeated stay of man in space. Under orbital conditions biological stress is induced in dry seeds of Arabidopsis thaliana by cosmic radiation especially its high energetic, densely ionizing component, the heavy ions (HZE). For comparison of radiation impact during different space flights a biological attempt at estimating the impact of single particles with high mass and energy (HZE-particles) on seeds was developed. Subdivision into LET-groups showed a remarkable contribution of an intermediate group (LET = 35 to 100 keV/micrometer) due to medium heavy ions (Z = 6 to 10). Efficiency factors for radiation damage experimentally determined and assigned to different LET-classes were compared to radiation quality factors discussed in literature.     

Biological monitoring of radiation exposure.

Complementary to physical dosimetry, biological dosimetry systems have been developed and applied which weight the different components of environmental radiation according to their biological efficacy. They generally give a record of the accumulated exposure of individuals with high sensitivity and specificity for the toxic agent under consideration. Basically three different types of biological detecting/ monitoring systems are available: (i) intrinsic biological dosimeters that record the individual radiation exposure (humans, plants, animals) in measurable units. For monitoring ionizing radiation exposure, in situ biomarkers for genetic (e.g. chromosomal aberrations in human lymphocytes, germ line minisatellite mutation rates) or metabolic changes in serum, plasma and blood (e.g. serum lipids, lipoproteins, lipid peroxides, melatonin, antibody titer) have been used. (ii) Extrinsic biological dosimeters/indicators that record the accumulated dose in biological model systems. Their application includes long-term monitoring of changes in environmental UV radiation and its biological implications as well as dosimetry of personal UV exposure. (iii) Biological detectors/biosensors for genotoxic substances and agents such as bacterial assays (e.g. Ames test, SOS-type test) that are highly sensitive to genotoxins with high specificity. They may be applicable for different aspects in environmental monitoring including the International Space Station.     

Initial approach to comparative studies on the evolutionary potentials of space radiation effects in a plant system.

The role of cosmic ionizing radiation, including heavy ions (HZE-particles) in the induction of mutations at the molecule-, chromosome-, genome- and cell-level is discussed on the basis of different DNA organization in a pro- and eukaryotically compartmented plant system (Arabidopsis thaliana (L.) Heynh.). Data recently obtained on the biological effects of ionizing radiation make it timely to discuss comparatively the evolutionary potentials of space radiation effects in the pro- and eukaryotic genomes (plasmon, plastidom, chondriom, and nucleom) during long duration exposure on space flights.     

Radiation safety standards: space hazards vs. terrestrial hazards.

The standards currently recommended for use in space travel were perhaps the first risk derived recommendations for dose limitations developed for quasi-occupational circumstances. They were based on data, considerations, and philosophy existing prior to 1970 and considered carcinogenesis primarily. In the intervening twelve years, not only has radiation risk information improved markedly but considerations relating to risk in general have become better known. The earlier recommendations have been examined with respect to changes in risk estimation and it is noted that the same philosophy used today, would probably lead to different dose limitations. However, other philosophies might be used; in particular a comparison of risks between terrestrial occupational radiation circumstances and also with fatal accident rates in a range of industries can be made and might be used in a modified philosophy with respect to risks from carcinogenesis. Developments have also taken place with respect to the knowledge of the biological effects of HZE particles but whether these effects are limiting as compared with radiation induced carcinogenesis is not yet clear. More studies on the effects of HZE particles, now becoming available, are needed. It is recommended that an in depth reexamination be undertaken of the biological effectiveness of space radiations and the philosophy of dose limitations in comparison with other risks.     

Interplanetary crew doses and dose equivalents: variations among different bone marrow and skin sites.

Previously, calculations of bone marrow dose from the large solar particle event (SPE) of July 2000 were carried out using the BRYNTRN space radiation transport code and the computerized anatomical man (CAM) model. Results indicated that the dose for a bone marrow site in the mid-thigh might be twice as large as the dose for a site in the pelvis. These large variations may be significant for space radiation protection purposes, which traditionally use an average of many (typically 33) sites throughout the body. Other organs that cover large portions of the body, such as the skin, may also exhibit similar variations with doses differing from site to site. The skin traditionally uses an average of 32 sites throughout the body. Variations also occur from site to site among the dose equivalents, which may be important in determining stochastic effects. In this work, the magnitudes of dose and dose equivalent variations from site to site are investigated. The BRYNTRN and HZETRN transport codes and the CAM model are used to estimate bone marrow and skin doses and dose equivalents as a function of position in the body for several large solar particle events and annual galactic cosmic ray spectra from throughout the space era. These position-specific results are compared with the average values usually used for radiation protection purposes. Various thicknesses of aluminum shielding, representative of nominal spacecraft, are used in the analyses.     

A review of instruments and methods for dosimetry in space

Instruments and methods recently used for space radiation dosimetry are reviewed for the purposes of comparison and reference. Passive detection methods mentioned include track-etch, luminescent, nuclear emulsion, and metal foil detectors. These can provide a reliable source of data for all types of radiation, but often require processing that cannot occur in space. Experimental methods of LET determination using TLDs, such as the high temperature peak ratio (HTR) method, are also discussed. Portable readout passive detectors including Pille, MOSFET, and bubble detector systems provide a novel alternative to traditional passive detectors, but research is more limited and their widespread use has yet to be established. Active detectors including DOSTEL, CPDS, RRMD-III, TEPC, R-16, BBND, and the Liulin series are examined for technical details. These instruments allow the determination of dose in real-time, and some can determine LET of incident particles by measuring energy deposition over a known path-length, but size and power consumption limit their practical use for dosimetry. Improved neutron dosimetry and development of a small active or portable readout personnel dosimeter capable of accurate LET determination are important steps for managing the effects of long-term exposure to the space radiation environment.     

Blood and small intestine cell kinetics under radiation exposures: Mathematical modeling

Mathematical models which describe the dynamics of two vital body systems (hematopoiesis and small intestinal epithelium) in mammals exposed to acute and chronic radiation are developed. These models, based on conventional biological theories, are implemented as systems of nonlinear differential equations. Their variables and constant parameters have clear biological meaning, that provides successful identification and verification of the models in hand. It is shown that the predictions of the models qualitatively and quantitatively agree with the respective experimental data for small laboratory animals (mice, rats) exposed to acute/chronic irradiation in wide ranges of doses and dose rates. The explanation of a number of radiobiological effects, including those of the low-level long-term exposures, is proposed proceeding from the modeling results. All this bears witness to the validity of employment of the developed models, after a proper identification, in investigation and prediction of radiation effects on the hematopoietic and small intestinal epithelium systems in various mammalian species, including humans. In particular, the models can be used for estimating effects of irradiation on astronauts in the long-term space missions, such as Lunar colonies and Mars voyages.     

Human response to high-background radiation environments on Earth and in space

The main long-term objective of the space exploration program is the colonization of the planets of the Solar System. The high cosmic radiation equivalent dose rate represents an inescapable problem for the safe establishment of permanent human settlements on these planets. The unshielded equivalent dose rate on Mars ranges between 100 and 200 mSv/year, depending on the Solar cycle and altitude, and can reach values as high as 360 mSv/year on the Moon. The average annual effective dose on Earth is about 3 mSv, nearly 85% of which comes from natural background radiation, reduced to less than 1 mSv if man-made sources and the internal exposure to Rn daughters are excluded. However, some areas on Earth display anomalously high levels of background radiation, as is the case with thorium-rich monazite bearing sand deposits where values 200–400 times higher than the world average can be found. About 2% of the world’s population live above 3 km and receive a disproportionate 10% of the annual effective collective dose due to cosmic radiation, with a net contribution to effective dose by the neutron component which is 3–4 fold that at sea level. Thus far, epidemiological studies have failed to show any adverse health effects in the populations living in these terrestrial high-background radiation areas (HBRA), which provide an unique opportunity to study the health implications of an environment that, as closely as possibly achievable on Earth, resembles the chronic exposure of future space colonists to higher-than-normal levels of ionizing radiation. Chromosomal aberrations in the peripheral blood lymphocytes from the HBRA residents have been measured in several studies because chromosomal damage represents an early biomarker of cancer risk. Similar cytogenetic studies have been recently performed in a cohort of astronauts involved in single or repeated space flights over many years. The cytogenetic findings in populations exposed to high dose-rate background radiation on Earth or in space will be discussed.     

Cellular changes in microgravity and the design of space radiation experiments.

Cell metabolism, secretion and cell-cell interactions can be altered during space flight. Early radiobiology experiments have demonstrated synergistic effects of radiation and microgravity as indicated by increased mutagenesis, increased chromosome aberrations, inhibited development, and retarded growth. Microgravity-induced changes in immune cell functions include reduced blastogenesis and cell-mediated, delayed-type hypersensitivity responses, increased cytokine secretions, but inhibited cytotoxic effects and macrophage differentiation. These effects are important because of the high radiosensitivity of immune cells. It is difficult to compare ground studies with space radiation biology experiments because of the complexity of the space radiation environment, types of radiation damage and repair mechanisms. Altered intracellular functions and molecular mechanisms must be considered in the design and interpretation of space radiation experiments. Critical steps in radiocarcinogenesis could be affected. New cell systems and hardware are needed to determine the biological effectiveness of the low dose rate, isotropic, multispectral space radiation and the potential usefulness of radioprotectants during space flight.