Radiation Hazards to Crews of Interplanetary Missions Biological Issues and Research Strategies (1996) / Chapter Skim
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2: Issues of Concern to NASA: Discussion and Conclusions
2: Issues of Concern to NASA: Discussion and Conclusions
Pages 13-34
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From page 13... ...
Although the possibility of catastrophic solar events, which could have short-term debilitating consequences despite the best countermeasures, cannot be excluded, observed solar events have not been in that category. Possible effects of exposure to radiation in space also include Pacifications of the lens of the eye, and synergistic effects arising from the microgravity environment cannot be excluded, but there is no evidence that these types of biological effects represent risks comparable with that of carcinogenesis.
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From page 14... ...
It is the combination of primary particles, attenuated primaries, and secondary particles at the biologically relevant site that determines the biological effects, not the primary spectrum per se. Galactic Cosmic Rays The major components of galactic cosmic radiation (OCR)
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1983 by Annual Reviews Inc. 15 Galactic cosmic rays are relatively constant in terms of distribution of particle types and energies over time, but they do decrease in intensity by roughly a factor of 10 during solar events because the increased energy emitted from the sun produces an increased interplanetary magnetic field that deflects a large fraction of the galactic cosmic rays.
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1991. Transport Methods and Interactions for Space Radiations.
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1995. Issues in space radiation protection: Galactic cosmic rays.
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Secondary Particles The broad distribution of the primary background radiation in space by particle type and energy has significant uncertainties at the lower energies, and significant variability is contributed by the uncertainty in the timing and intensity of solar events. However, a major uncertainty in estimating space radiation's harmful effects for space crews is the uncertainty of the actual particle distribution at the point of exposure of crew members inside a spacecraft, inside a space suit for crew members conducting extravehicular activities, or actually at the sites of specific organs of crew members.
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From page 19... ...
Thus, significant risks for experiencing early effects occur only with very high radiation fluences. Radiation Environment Because of the deterministic nature of early effects, it is likely that radiation arising from HZE particles and background cosmic radiation would pose no significant risk of early deleterious biological effects for spacecraft crew members.
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From page 20... ...
Thus the risk estimates described below are derived from rather extensive data on effects of low-LET radiation, given that very few data are available on the incidence of such early effects following whole-body proton irradiation. It should be noted that there has been no evidence for new or qualitatively different early effects arising from proton irradiation per se that would lead to uncertainty in the prediction of early biological effects in space.
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From page 21... ...
Skin damage would occur only in crew members working outside the spacecraft during an SPE. Late Effects General Considerations Potentially important late effects following exposure to radiation during spaceflight include induction of cancer and damage to the central nervous system (CNS)
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From page 22... ...
, the radiation environment in deep space consists principally of galactic cosmic rays composed of protons, helium ions, and, to a lesser extent, heavy ions rather than the mainly low-LET radiation to which atomic bomb survivors were exposed. For the most part, radiation in space occurs at a low fluence rate.
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From page 23... ...
The limited dose-response data that can be obtained from these studies suggest similarities to responses that would be seen after gamma ray irradiation.37~39 Only one study found evidence to support an RBE of greater than 1.40 Additional support for similarities in effects from exposure to proton and to low-LET radiation comes from the work of Burns et al., who have reported a curvilinear dose response for rat skin tumor induction similar to that occurring after exposure to electrons and a reduction in the carcinogenic effects of exposure to protons.4i Cellular studies have been conducted using protons of different energies to examine cell survival and induction of chromosomal aberrations.42~45 Although the range of energies used is lower than that encountered in the space environment, these data also suggest similarities in effects between protons, gamma rays, and x rays. The dose responses tend to be linear/quadratic, and there is clear evidence for repair of protoninduced DNA damage.
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From page 24... ...
Studies of Harderian gland tumorigenesis also suggest that the RBE values for fission spectrum neutrons are similar to those for 100- to 200-keV/,um heavy ions. 48 If this is the case, there are dose-response and dose rate data for the induction of several tumors in mice after neutron irradiation that could be used in support of establishing a reliable quality factor for heavy ions in this energy range.49 While not able to be used directly for the derivation of quality factors, studies of cells have provided evidence that for high-LET radiation, linear dose-response relationships are only slightly influenced by fractionation or protraction.50~52 In addition, studies of mutagenesis and induction of chromosomal aberrations suggest possible qualitative as well as quantitative differences between high- and low-LET radiation and different particle types of the same LET that need to be examined further for their applicability to understanding cancer risks.53 54 Of these, it is important to note the recent observations of high-LET radiation effects on chromosome instability and the induction of delayed radiation damage leading to expression of damage in the progeny of surviving irradiated cells.55 Conclusions The present state of knowledge regarding cancer induction by irradiation, as described above, requires that additional research be directed in two areas.
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From page 25... ...
1989. Extrapolations of rat skin tumor incidence: Dose, fractionation and linear energy transfer.
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Lack of Data for Estimating Risks The reason for concern regarding the CNS is due to the fact that it cannot be stated with confidence what late effects, if any, might occur in the CNS of humans exposed to the various types of radiation in space such as heavy ions and secondaries of the more prevalent protons. There is evidence that in photoreceptors iron ions cause an increased loss of DNA.59 Whether a significant interaction occurs between aging and radiation-damaged cells (which is suggested by at least one investigator60)
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From page 27... ...
In humans, a threshold dose for low-LET radiation of about 2.0 Gy has been considered reasonable. For the atomic bomb survivors, a somewhat lower threshold dose, 1.0 to 1.5 Gy, was derived by Otake and Schu11.68 Since these results pertain to high-dose-rate exposures, it is important to know the reduction in effect that may result from fractionation or from lowering of the dose rate.
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From page 28... ...
Variation in Susceptibility to Radiation Across Subject Types The rapid increase in knowledge of the mechanisms of tumor induction and heritable effects has led to a clear appreciation of the potential for a genetic predisposition to the induction of cancer by exogenous agents and endogenous processes and to induction of heritable changes. Such a predisposition might be specific for a single agent such as ionizing radiation (e.g., predisposition in ataxia telangiectasia heterozygotes)
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From page 29... ...
DNA Repair The repair mechanisms utilized by the human body after exposure to radiation are an important part of any discussion of radiation effects, and the repair of damage to DNA is of obvious interest when considering late effects such as cancer. It has been known for a number of years that sophisticated and complex cellular processes exist for repairing all types of DNA damage: single-strand breaks, double-strand breaks, and a wide variety of types of base damage, all of which can result from exposure to radiation.
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From page 30... ...
It has been suggested that there could be a link between double-strand break repair machinery and transcription, as has been described for NER.93 A preferential repair of ionizing radiation-induced DNA damage on the transcribed strand has recently been described,94 and DNA-PK is a potent inhibitor of transcription by RNA polymerase 1.95 On the basis of these mechanistic studies, it is predicted that there will be a range of individual sensitivities to ionizing radiation that is, in part, dependent on the efficiency of the repair processes for double-strand breaks. To date, no human syndromes that are characterized by defects in DNA-PK have been identified, although the DNA-PKCs gene maps to the same human chromosome region as the one for the human gene that complements scid.96 Other Studies A good deal has been learned about repair mechanisms by studying the human syndrome ataxia telangiectasia (AT)
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From page 31... ...
Thus, heterozygosity for DNA repair genes, where the phenotype is not immediately apparent, could be a marker for susceptibility to cancer, particularly following exposure to ionizing radiation. It is expected that screening for ATM heterozygosity will soon be possible based on recent reports of the genomic organization and gene sequence.~04 i05 Conclusion A growing understanding of the various mechanisms of repair of ionizing radiation-induced DNA damage, and of the effects of mutations in genes involved in the repair itself or in its control, is likely to greatly aid in predicting the risk of adverse biological effects arising from exposure to radiation, and eventually in identifying individuals at increased risk.
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From page 32... ...
1988. Study of Biological Effects and Radiation Protection to Future European Manned Space Flights.
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From page 33... ...
Galactic cosmic rays and cell-hit frequencies outside the magnetosphere.
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From page 34... ...
1993. Sources and Effects of Ionizing Radiation: United Nations Committee on the Effects of Atomic Radiation: UNSCEAR 1993 Report to the General Assembly, with scientific annexes.
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