A comparison of quality factors and weighting factors for characterizing astronaut radiation exposures.

Radiation exposures are typically characterized by two quantities. The first is the absorbed dose, or the energy deposited per unit mass for specific types of radiation passing through specified materials. The same amount of energy deposited in material by two different types of radiation, however, can result in two different levels of risk. Because of this, for the purpose of radiation protection operations, absorbed dose is modified by a second factor intended to normalize the risk associated with a given exposure. We present here an inter-comparison of methods for this modification. First is the radiation quality factor (Q), as defined by ICRP publication 60. This quantity is related functionally to the unrestricted linear energy transfer (LET) of a given radiation, and is multiplied by the absorbed dose to derive the dose equivalent (H). The second method for modifying absorbed dose is the radiation weighting factor, also given in ICRP-60, or as modified in NCRP report 115. To implement the weighting factor, the absorbed dose resulting from incidence of a particular radiation is multiplied by a factor assigned to that type of radiation, giving the equivalent dose. We compare calculations done based on identical fields of radiation representative of that encountered by the MIR space station, applying each of these two methods.     

Genetic risks associated with radiation exposures during space flight.

The genetic risks associated with manned space flight are judged to be of little significance to the general population. The risks may be significant to the irradiated individual, particularly if one focuses attention on the incidence of dominant and chromosomal mutations that are expressed in the first generation offspring. Even so, the risk is not increased to a great extent by the low linear energy transfer (LET) component of the space radiations. It is the presumed high LET component, neutrons especially, that would make the major contribution to the risk, because the relative biological effectiveness (RBE) values for this component, relative to low dose-rate photon irradiation, are between 10 and 40, depending upon the particular genetic effect and dose-rate comparison. The appropriate RBE value would probably be 20 or greater, so that even small neutron doses become magnified in their contribution. Under the assumed condition of protracted exposure to 8 rads of low LET radiation and 2 rads of high LET radiation, or from 48 to 88 rem, the individual's risk of transmitting a new dominant mutation that will be expressed in his immediate offspring is estimated to increase by at least 4% and as much as about 40%. The HZE-particle component is not expected to make a significant contribution to the total risk.     

Fragmentation of 1 GeV/nucleon iron ions in thick targets relevant for space exploration.

We have measured charged nuclear fragments produced by 1 GeV/nucleon 56Fe ions interacting with aluminium, polyethylene and lead. These materials are relevant for assessment of radiation risk for manned space flight. The data will be presented in a form suitable for comparison with models of nuclear fragmentation and transport, including linear energy transfer (LET) spectrum, fluence for iron and fragments, event-tack- and event-dose-averaged LET, total dose and iron contribution to dose.     

Chromosome aberration yields and apoptosis in human lymphocytes irradiated with Fe-ions of differing LET.

In the present paper the relationship between cell cycle delays induced by Fe-ions of differing LET and the aberration yield observable in human lymphocytes at mitosis was examined. Cells of the same donor were irradiated with 990 MeV/n Fe-ions (LET=155 keV/micrometers), 200 MeV/n Fe-ions (LET=440 keV/micrometers) and X-rays and aberrations were measured in first cycle mitoses harvested at different times after 48-84 h in culture and in prematurely condensed G2-cells (PCCs) collected at 48 h using calyculin A. Analysis of the time-course of chromosomal damage in first cycle metaphases revealed that the aberration frequency was similar after X-ray irradiation, but increased two and seven fold after exposure to 990 and 200 MeV/n Fe-ions, respectively. Consequently, RBEs derived from late sampling times were significantly higher than those obtained at early times. The PCC-data suggest that the delayed entry of heavily damaged cells into mitosis results especially from a prolonged arrest in G2. Preliminary data obtained for 4.1 MeV/n Cr-ions (LET=3160 keV/micrometers) revealed, that these delays are even more pronounced for low energy Fe-like particles. Additionally, for the different radiation qualities, BrdU-labeling indices and apoptotic indices were determined at several time-points. Only the exposure to low energy Fe-like particles affected the entry of lymphocytes into S-phase and generated a significant apoptotic response indicating that under this particular exposure condition a large proportion of heavily damaged cells is rapidly eliminated from the cell population. The significance of this observation for the estimation of the health risk associated with space radiation remains to be elucidated.     

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.     

Early and late mammalian responses to heavy charged particles.

This overview summarizes murine results on acute lethality responses, inactivation of marrow CFU-S and intestinal microcolonies, testes weight loss, life span shortening, and posterior lens opacification in mice irradiated with heavy charged particles. RBE-LET relationships for these mammalian responses are compared with results from in vitro studies. The trend is that the maximum RBE for in vivo responses tends to be lower and occurs at a lower LET than for inactivation of V79 and T-1 cells in culture. Based on inactivation cross sections, the response of CFU-S in vivo conforms to expectations from earlier studies with prokaryotic systems and mammalian cells in culture. Effects of heavy ions are compared with fission spectrum neutrons, and the results are consistent with the interpretation that RBEs are lower than for fission neutrons at about the same LET, probably due to differences in track structure. Issues discussed focus on challenges associated with assessments of early and late effects of charged particles based on dose, RBE and LET, and with the concordance or discordance of results obtained with in vivo and in vitro model systems. Models for radiation damage/repair and misrepair should consider effects observed with in vivo as well as in vitro model systems.     

Estimation of risk based on multiple events in radiation carcinogenesis of rat skin.

In the multistage theory of carcinogenesis, cells progress to cancer through a series of discrete, irreversible, heritable genetic alterations or mutations. However data on radiation-induced cancer incidence in rat skin suggests that some part of an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to the following radiations: 1. an electron beam (LET=0.34 keV/um, 2. a neon ion beam (LET=25 keV/um and 3. an argon ion beam (LET=125 keV/um. The latter 2 beams were generated by the Bevalac at the Lawrence Berkeley Laboratory, Berkeley, CA. About 6.0 cm2 of skin was irradiated per rat. The rats were observed every 6 weeks for at least 78 weeks and tumors were scored at first occurrence. Several histological types of cancer, including squamous and basal cell carcinomas, were induced. The cancer yield versus radiation dose was fitted by the quadratic equation (Y(D)=CLD+BD2), and the parameters C and B were estimated for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated in all tumors tested, although only a small proportion of neon-induced tumors showed similar activation. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable, linked event pathway at high LET; either pathway may advance the cell by 1 stage in the multistage model. The model, if validated, permits the direct calculation of cancer risk in rat skin in a way that can be subjected to experimental testing.     

Late skin damage in rabbits and monkeys after exposure to particulate radiations.

Skin biopsies were taken from the central regions of the ears of New Zealand white rabbits following localized exposure of one ear of each rabbit to 530 MeV/amu Ar or 365 MeV/amu Ne ions. The unirradiated ears served as controls. Biopsies were taken also from the chests and inner thighs of rhesus monkeys after whole-body exposure to 32 MeV protons and from unirradiated control animals. The linear energy transfers (LET infinity's) for the radiations were 90 +/- 5, 35 +/- 3, and approximately 1.2 keV/micrometer, respectively. In the rabbit studies, explants were removed with a 2 mm diameter dermal punch at post-irradiation times up to five years after exposure. Similar volumes of monkey tissue were taken from skin samples excised surgically 16-18 years following proton irradiation. Fibroblast cultures were initiated from the explants and were propagated in vitro until terminal senescence (cessation of cell division) occurred. Cultures from irradiated tissue exhibited decreases in doubling potential that were dependent on radiation dose and LET infinity and seemed to reflect damage to stem cell populations. The implications of these results for astronauts exposed to heavy ions and/or protons in space include possible manifestations of residual effects in the skin many years after exposure (e.g. unsatisfactory responses to trauma or surgery).     

Radiation measured during ISS-Expedition 13 with different dosimeters

Radiation in low Earth orbit (LEO) is mainly composed of galactic cosmic rays (GCR), solar energetic particles and particles in SAA (South Atlantic Anomaly). The biological impact of space radiation to astronauts depends strongly on the particles’ linear energy transfer (LET) and is dominated by high LET radiation. It is important to measure the LET spectrum for the space radiation field and to investigate the influence of radiation on astronauts. At present, the preferred active dosimeters sensitive to all LET are the tissue equivalent proportional counter (TEPC) and the silicon detectors in various configurations; the preferred passive dosimeters are CR-39 plastic nuclear track detectors (PNTDs) sensitive to high LET and thermoluminescence dosimeters (TLDs) as well as optically stimulated luminescence dosimeters (OSLDs) sensitive to low LET. The TEPC, CR-39 PNTDs, TLDs and OSLDs were used to investigate the radiation field for the ISS mission Expedition 13 (ISS-12S) in LEO. LET spectra and radiation quantities (fluence, absorbed dose, dose equivalent and quality factor) were measured for the space mission with different dosimeters. This paper introduces the role of high LET radiation in radiobiology, the operational principles for the different dosimeters, the LET spectrum method using CR-39 detectors, the method to combine the results measured with TLDs/OSLDs and CR-39 PNTDs, and presents the LET spectra and the radiation quantities measured and combined.     

Induction and repair of DNA strand breaks in bovine lens epithelial cells after high LET irradiation.

The lens epithelium is the initiation site for the development of radiation induced cataracts. Radiation in the cortex and nucleus interacts with proteins, while in the epithelium, experimental results reveal mutagenic and cytotoxic effects. It is suggested that incorrectly repaired DNA damage may be lethal in terms of cellular reproduction and also may initiate the development of mutations or transformations in surviving cells. The occurrence of such genetically modified cells may lead to lens opacification. For a quantitative risk estimation for astronauts and space travelers it is necessary to know the relative biological effectiveness (RBE), because the spacial and temporal distribution of initial physical damage induced by cosmic radiation differ significantly from that of X-rays. RBEs for the induction of DNA strand breaks and the efficiency of repair of these breaks were measured in cultured diploid bovine lens epithelial cells exposed to different LET irradiation to either 300 kV X-rays or to heavy ions at the UNILAC accelerator at GSI. Accelerated ions from Z=8 (O) to Z=92 (U) were used. Strand breaks were measured by hydroxyapatite chromatography of alkaline unwound DNA (overall strand breaks). Results showed that DNA damage occurs as a function of dose, of kinetic energy and of LET. For particles having the same LET the severity of the DNA damage increases with dose. For a given particle dose, as the LET rises, the numbers of DNA strand breaks increase to a maximum and then reach a plateau or decrease. Repair kinetics depend on the fluence (irradiation dose). At any LET value, repair is much slower after heavy ion exposure than after X-irradiation. For ions with an LET of less than 10,000 keV micrometers-1 more than 90 percent of the strand breaks induced are repaired within 24 hours. At higher particle fluences, especially for low energetic particles with a very high local density of energy deposition within the particle track, a higher proportion of non-rejoined breaks is found, even after prolonged periods of incubation. At the highest LET value (16,300 keV micrometers-1) no significant repair is observed. These LET-dependencies are consistent with the current mechanistic model for radiation induced cataractogenesis which postulates that genomic damage to the surviving fraction of epithelial cells is responsible for lens opacification.     

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.     

Late effects from particulate radiations in primate and rabbit tissues.

Optic tissues in groups of New Zealand white rabbits were irradiated locally at different stages throughout the median life span of the species with a single dose (9 Gy) of 425 MeV/amu Ne ions (LET infinity approximately 30 keV/micrometer) and then inspected routinely for the progression of radiation cataracts. The level of early cataracts was found to be highest in the youngest group of animals irradiated (8 weeks old), but both the onset of late cataracts and loss of vision occurred earlier when animals were irradiated during the second half of the median life span. This age response can have serious implications in terms of space radiation hazards to man. Rhesus monkeys that had been subjected to whole-body skin irradiation (2.8 and 5.6 Gy) by 32 MeV protons (range in tissue approximately 1 cm) some twenty years previously were analysed for radiation damage by the propagation of skin fibroblasts in primary cultures. Such propagation from skin biopsies in MEM-alpha medium (serial cultivation) or in supplemented Ham's F-10 medium (cultivation without dilution) revealed late damage in the stem (precursor) cells of the skins of the animals. The proton fluxes employed in this experiment are representative of those occurring in major solar flares.     

Effect of heavy ions on neuro-endocrine regulations.

During American and Russian short and long-term space flights neuroimmune dysregulations have been observed in man and rats for up to three months after the return. During Extra-Vehicular Activity, radiation exposure risk is greater to elicit short and/or long-term deleterious effects on the functional capacity of the neuroimmune system. In order to assess the effects of high LET events on neuroimmune networks, our preliminary ground-based study was to investigate brain inflammatory responses in mouse after low dose radiation exposure with high LET particles (12C, 95MeV/u, 42 mGy). Plasma corticosterone levels were rapidly (6 hours) increased by two-fold, then decreased 24 hours post-irradiation. At 3 days plasma corticosterone and ACTH concentrations were also two- to three-fold increased. Plasma ACTH levels were still elevated up to seven days to two months. Furthermore immune functions are under current assessment. The results of this study should allow a greater understanding of the effects of high LET particles on neuroimmune system.     

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.     

The influence of dose, dose-rate and particle fragmentation on cataract induction by energetic iron ions.

Because activities in space necessarily involve chronic exposure to a heterogeneous charged particle radiation field it is important to assess the influence of dose-rate and the possible modulating role of heavy particle fragmentation on biological systems. Using the well-studied cataract model, mice were exposed to plateau 600 MeV/amu 56Fe ions either as acute or fractionated exposures at total doses of 5 - 504 cGy. Additional groups of mice received 20, 360 and 504 cGy behind 50 mm of polyethylene, which simulates body shielding. The reference radiation consisted of 60Co gamma radiation. The animals were examined by slit lamp biomicroscopy over their three year life spans. In accordance with our previous observations with heavy particles, the cataractogenic potential of the 600 MeV/amu 56Fe ions was greater than for low-LET radiation and increased with decreasing dose relative to gamma-rays. Fractionation of a given dose of 56Fe ions did not reduce the cataractogenicity of the radiation compared to the acute regimen. Fragmentation of the beam in the polyethylene did not alter the cataractotoxicity of the ions, either when administered singly or in fractions.     

Austrian dose measurements onboard space station MIR and the International Space Station--overview and comparison.

The Atominstitute of the Austrian Universities has conducted various space research missions in the last 12 years in cooperation with the Institute for Biomedical Problems in Moscow. They dealt with the exact determination of the radiation hazards for cosmonauts and the development of precise measurement devices. Special emphasis will be laid on the last experiment on space station MIR the goal of which was the determination of the depth distribution of absorbed dose and dose equivalent in a water filled Phantom. The first results from dose measurements onboard the International Space Station (ISS) will also be discussed. The spherical Phantom with a diameter of 35 cm was developed at the Institute for Biomedical Problems and had 4 channels where dosimeters can be exposed in different depths. The exposure period covered the timeframe from May 1997 to February 1999. Thermoluminescent dosimeters (TLDs) were exposed inside the Phantom, either parallel or perpendicular to the hull of the spacecraft. For the evaluation of the linear energy transfer (LET), the high temperature ratio (HTR) method was applied. Based on this method a mean quality factor and, subsequently, the dose equivalent is calculated according to the Q(LET infinity) relationship proposed in ICRP 26. An increased contribution of neutrons could be detected inside the Phantom. However the total dose equivalent did not increase over the depth of the Phantom. As the first Austrian measurements on the ISS dosimeter packages were exposed for 248 days, starting in February 2001 at six different locations onboard the ISS. The Austrian dosimeter sets for this first exposure on the ISS contained five different kinds of passive thermoluminescent dosimeters. First results showed a position dependent absorbed dose rate at the ISS.     

RBE: mechanisms inferred from cytogenetics.

Cyclotron-accelerated heavy ion beams provide a fine degree of control over the physical parameters of radiation. Cytogenetics affords a view into the irradiated cell at the resolution of chromosomes. Combined they form a powerful means to probe the mechanisms of RBE. Cytogenetic studies with high energy heavy ion beams reveal three LET-dependent trends for 1) level of initial damage, 2) distribution of damage among cells, and 3) lesion severity. The number of initial breaks per unit dose increases from a low-LET plateau to a peak at approximately 180 keV/micrometer and declines thereafter. Overdispersion of breaks is significant above approximately 100 keV/micrometer. Lesion severity, indicated by the level of chromosomal fragments that have not restituted even after long repair times, increases with LET. Similar studies with very low energy 238Pu alpha particles (120 keV/micrometer) reveal higher levels of initial breakage per unit dose, fewer residual fragments and a higher level of misrepair when compared to high energy heavy ions at the same LET. These observations would suggest that track structure is an important factor in genetic damage in addition to LET.     

Summary of current radiation dosimetry results on manned spacecraft.

Measurements of radiation exposures aboard manned space flights of various altitudes, orbital inclinations and durations were performed by means of passive radiation detectors, thermoluminescent detectors (TLD's), and in some cases by active electronic counters. The TLD's and electronic counters covered the lower portion of the LET (linear energy transfer) spectra, while the nuclear track detectors measured high-LET produced by HZE particles. In Spacelab (SL-1), TLD's recorded a range of 102 to 190-millirad, yielding an average low-LET dose rate of 11.2 mrad per day inside the module, about twice the dose rate measured on previous space shuttle flights. Because of a higher inclination of the SL-1 orbit (57 degrees versus 28.5 degrees for previous shuttle flights), substantial fluxes of highly ionizing HZE particles were also observed, yielding an overall average mission dose-equivalent of about 135 millirem, about three times higher than measured an previous shuttle missions. A dose rate more than an order of magnitude higher than for any other space shuttle light was obtained for mission STS-41C, reflecting the highest orbital altitude to date of 519 km.