The evolution of nucleotides.

There has been much speculation about the types of molecules that were present in the first living forms. Recent discoveries show that RNA is a more versatile molecule than was previously believed, but whether it was ever able, for example, to synthesize its own monomers from available precursors is not yet known. If amino acids coexisted with nucleosides on the prebiotic Earth, then it seems likely that these two classes of molecules would have interacted with each other. We have been studying oligonucleotide-directed peptide bond formation, and during this work we discovered that aminoacylation of the internal 2'-hydroxyl groups of RNA occurred stereoselectively. Investigation of the mechanism of this reaction has been aided by the use of 3'-inosine methyl phosphate (as a simplified model for a dinucleoside monophosphate) and proton nmr spectroscopy of t-butoxycarbonyl-alanyl esters of nucleosides as models for the transition state of the aminoacylation reaction itself.     

Prebiotic synthesis and reactions of nucleosides and nucleotides.

Diiminosuccinonitrile (DISN) has been investigated as a potential prebiotic phosphorylating agent. It is formed readily by the oxidation of diaminomaleonitrile (DAMN), a tetramer of HCN. DISN effects the cyclization of 3'-adenosine monophosphate to adenosine 2',3'-cyclic phosphace in up to 40% yield. The DISN-mediated phosphorylation of uridine to uridine mono-phosphate does not proceed efficiently in aqueous solution. The reaction of DISN and BrCN with uridine-5'-phosphate and uridine results in the formation of 2,2'-anhydronucleotides and 2,2'-anhydronucleosides respectively, and other reaction products resulting from an initial reaction at the 2'- and 3'-hydroxyl groups. The clay mineral catalysis of the cyclization of adenosine-3'-phosphate was investigated using homoionic montmorillonites.     

Radiation risk and human space exploration.

Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented.     

Radiation risk during long-term spaceflight.

Cosmonauts' exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members' lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration.     

Radiation exposures during space flight and their measurement.

The paper reviews radiation exposures recorded during space flights of the US and USSR. Most of the data are from manned missions and include discussion of absorbed dose and dose rates as a function of parameters such as altitude, inclination, spacecraft type and shielding. Preliminary data exist on the neutron and HZE-particle component, as well as the LET spectra. For low Earth-orbit missions, the dose encountered is strongly altitude-dependent, with a weaker dependence upon inclination. The doses range from about 6 millirad per day for the Space Transportation System No. 3 flight to about 90 mrad per day for Skylab. The effective quality factor (QF) for the near-Earth orbits and free space has been estimated to be about 1.5 and about 5.5 respectively. Complete shielding from the galactic cosmic rays does not appear practical because of spacecraft weight limitations.     

Radiation chemistry of the hippocampal brain slice.

The in vitro hippocampal brain slice is a 0.4 mm thick neural network that can be used to study brain responses to radiation and related injuries. This preparation is unique in that it responds to ionizing radiation within minutes after exposure without complications from changes in vascularity, blood flow, blood pressure, etc. Electrophysiological studies have shown that x- and gamma-rays alter synaptic transmission and spike generation, elements of normal brain activity. To evaluate the role of hydroxyl free radicals (OH) in these changes, slices were exposed to dilute H2O2 solutions. EPR spin trapping experiments verified that OH is produced. Neural responses, while similar, were not identical to those due to radiation, possibly because of a different distribution of OH. Although H2O2 is freely diffusible, it produces OH at specific sites where, e.g. iron reduces it. In contrast, x- and gamma-rays produce OH more uniformly throughout the tissue. H2O2 may provide a better model for high-LET radiation where yields of radical products of water radiolysis are decreased and peroxide reactions predominate.     

Radiation biodosimetry: applications for spaceflight.

The multiparametric dosimetry system that we are developing for medical radiological defense applications could be adapted for spaceflight environments. The system complements the internationally accepted personnel dosimeters and cytogenetic analysis of chromosome aberrations, considered the best means of documenting radiation doses for health records. Our system consists of a portable hematology analyzer, molecular biodosimetry using nucleic acid and antigen-based diagnostic equipment, and a dose assessment management software application. A dry-capillary tube reagent-based centrifuge blood cell counter (QBC Autoread Plus, Becton [correction of Beckon] Dickinson Bioscience) measures peripheral blood lymphocytes and monocytes, which could determine radiation dose based on the kinetics of blood cell depletion. Molecular biomarkers for ionizing radiation exposure (gene expression changes, blood proteins) can be measured in real time using such diagnostic detection technologies as miniaturized nucleic acid sequences and antigen-based biosensors, but they require validation of dose-dependent targets and development of optimized protocols and analysis systems. The Biodosimetry Assessment Tool, a software application, calculates radiation dose based on a patient's physical signs and symptoms and blood cell count analysis. It also annotates location of personnel dosimeters, displays a summary of a patient's dosimetric information to healthcare professionals, and archives the data for further use. These radiation assessment diagnostic technologies can have dual-use applications supporting general medical-related care.     

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.     

Abiogenic synthesis of pyrimidine nucleotides in solid state by vacuum ultraviolet radiation.

The abiogenic synthesis of pyrimidine nucleotides in solid state has been investigated. Our experiment indicates that natural nucleotides are produced in thin films prepared from nucleoside and inorganic phosphate by irradiating with vacuum ultraviolet light (VUV, lambda=100-200 nm). We have investigated the influence of the type of nucleic acids base (thymidine, cytosine, uracil) and the structure of sugar moiety (ribose or deoxyribose) on the course and yield of reaction. We compared the action of vacuum ultraviolet light with action of gamma-radiation, heat and biology significant UV (254 nm) which have been investigated earlier. The occurrence of these reaction in open space is discussed.     

Radiation measurements on the flight of IML-2.

The second flight of the International Microgravity Laboratory (IML-2) on Space Shuttle flight STS-65 provided a unique opportunity for the intercomparison of a wide variety of radiation measurement techniques. Although this was not a coordinated or planned campaign, by sheer chance, a number of space radiation experiments from several countries were flown on this mission. There were active radiation measuring instruments from Japan and US, and passive detectors from US, Russia, Japan, and Germany. These detectors were distributed throughout the Space Shuttle volume: payload bay, middeck, flight deck, and Spacelab. STS-65 was launched on July 8, 1994, in a 28.45 degrees x 306 km orbit for a duration of 14 d 17 hr and 55 min. The crew doses varied from 0.935 mGy to 1.235 mGy. A factor of two variation was observed between various passive detectors mounted inside the habitable Shuttle volume. There is reasonable agreement between the galactic cosmic ray dose, dose equivalent and LET spectra measured by the tissue equivalent proportional counter flown in the payload bay with model calculations. There are significant differences in the measurements of LET spectra measured by different groups. The neutron spectrum in the 1-20 MeV region was measured. Using fluence-dose conversion factors, the neutron dose and dose equivalent rates were 11 +/- 2.7 microGy/day and 95 +/- 23.5 microSv/day respectively. The average east-west asymmetry of trapped proton (>3OMeV) and (>60 MeV) dose rate was 3.3 and 1.9 respectively.     

Radiation quality and risk estimation in relation to space missions.

While Q is specified as a function of linear energy transfer (LET) in practice the Q for neutrons has been selected by a judgment decision based on the relative biological effectiveness (RBE) to induce stochastic effects. There are no RBE values for tumor induction by heavy ions or protons in humans. Thus, selection of Q values has been based either on LET (or lineal energy) or RBEs from animal experiments. Estimates of Q for heavy ions in low earth orbit (LEO) range from about 5 to 14. The average Q value of all radiation in LEO has been estimated to be about 1.3. There is a lack of experimental data for RBEs for heavy ions but RBE increases as a function of LET. In the case of the Harderian gland the RBE reaches a maximum of 25-30 between about 100-200 keV/micrometer but does not appear to decrease at higher LETs. The International Commission of Radiological Protection have proposed the use of radiation weighting factors in lieu of quality factors. The weighting factors will range from 1 to 20.     

Prebiotic synthesis of nucleotides at the Earth orbit in presence of Lunar soil.

Modern studies now favor the fact that extraterrestrial organic molecules served as an important source of biological important substances on the primitive Earth. It is presumed that these space-made organic molecules could be transported safely to the Earth surface being associated with mineral grains. It is important to test whether nucleotides synthesized in Earth orbit could be protected by lunar surface regolite. The phosphorylation of adenosine, uridine and thymidine has been studied with respect of their further transformations and degradation in presence of mineral bed. After retrieval, HPLC analysis is used to identify all the mononucleotides of certain nucleosides. It has been shown, that exposure of the investigated nucleosides as dry films in space conditions in the presence of Lunar soil increases the yield of synthesized nucleotides in 1.1-3.0 times as compared with the exposure of the same samples in absence of Lunar soil. To identify and evaluate the principal source of energy in open space responsible for nucleotide synthesis reaction laboratory experiments were performed. It has been shown, that vacuum ultra violet (VUV 145 nm) radiation promotes nucleotide synthesis more effectively than ultra violet (UV 254 nm) while the presence of Lunar soil increases reaction yield in 1.5-2.0 times. Formation of 5'-mononucleotides seemed to be the most effective reaction both in flight and in laboratory experiments. Protective action of lunar soil on synthesized nucleotides against UV radiation has been shown in open Space conditions.     

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.     

Long-term modulation of Galactic Cosmic Radiation and its model for space exploration.

As the human exploration of space has received new attention in the United States, studies find that exposure to space radiation could adversely impact the mission design. Galactic Cosmic Radiation (GCR), with its very wide range of charges and energies, is particularly important for a mission to Mars, because it imposes a stiff mass penalty for spacecraft shielding. Dose equivalent versus shielding thickness calculations, show a rapid initial drop in exposure with thickness, but an asymptotic behavior at a higher shielding thickness. Uncertainties in the radiobiology are largely unknown. For a fixed radiation risk, this leads to large uncertain ties in shielding thickness for small uncertainties in estimated dose. In this paper we investigate the application of steady-state, spherically-symmetric diffusion-convection theory of solar modulation to individual measurements of differential energy spectra from 1954 to 1989 in order to estimate the diffusion coefficient, kappa (r,t), as a function of time. We have correlated the diffusion coefficient to the Climax neutron monitor rates and show that, if the diffusion coefficient can be separated into independent functions of space and time: kappa (-r,t)=K(t)kappa 0 beta P kappa 1(r), where beta is the particle velocity and P the rigidity, then (i) The time dependent quantity 1/K(t), which is proportional to the deceleration potential, phi(r,t), is linearly related to the Climax neutron monitor counting rate. (ii) The coefficients obtained from hydrogen or helium intensity measurements are the same. (iii) There are different correlation functions for odd and even solar cycles. (iv) The correlation function for the Climax neutron monitor counting rate for given time, t, can be used to estimate mean deceleration parameter phi(t) to within +/- 15% with 90% confidence. We have shown that kappa(r,t) determined from hydrogen and/or helium data, can be used to fit the oxygen and iron differential energy spectra with a root mean square error of about +/- 10%, and essentially independent of the particle charge or energy. We have also examined the ion chamber and 14C measurements which allow the analysis to be extended from the year 1906 to 1990. Using this model we have defined reference GCR spectra at solar minimum and solar maximum. These can be used for space exploration studies and provide a quantitative estimate of the error in dose due to changes in GCR intensities.     

Radiation protection guidance for activities in low-Earth orbit.

Scientific Committee 75 (SC 75) of the National Council on Radiation Protection and Measurements (NCRP) was assembled for the purpose of providing guidance to NASA concerning radiation protection in low-Earth orbit. The report of SC 75 was published in December 2000 as NCRP Report No. 132. In this presentation an overview of the findings and recommendations of the committee report will be presented.     

Radiation biology in space: a critical review.

A short summary of the results of radiobiological studies in space or on respective particles on ground will be given. Among the various types of radiation in space, the effect of heavy ions with high energy (HZE-particles) are most essential. Thus, radiobiology in space concerns mostly to the effect of these particles, in cells and in whole organism. Cell death, mutation and malignant transformation are the relevant endpoints, with can be studied on ground with heavy ions of different energy with suitable accelerators or in space, especially by the BIOSTACK concept. In space, however, the effect of microgravity has to be considered as well and there are hints, that under weightlessness the biological effect of radiation may be enhanced. There are still open questions to be answered concerning radioprotection of man in space. Further experiments are necessary.     

Radiation environment monitoring for manned missions to Mars.

In this paper a radiation monitoring system for manned Mars missions is described, based on the most recent requirements on crew radiation safety. A comparison is shown between the radiation monitoring systems for Earth-orbiting and interplanetary spacecraft, with similarities and differences pointed out and discussed. An operational and technological sketch of the chosen problem solving approach is also given.     

Radiation hazards on space missions outside the magnetosphere.

Future space missions outside the magnetosphere will subject astronauts to a hostile and unfamiliar radiation environment. An annual dose equivalent to the blood-forming organs (BFOs) of approximately 0.5 Sv is expected, mostly from heavy ions in the galactic cosmic radiation. On long-duration missions, an anomalously-large solar energetic particle event may occur. Such an event can expose astronauts to up to approximately 25 Gy (skin dose) and up to approximately 2 Sv (BFO dose) with no shielding. The anticipated radiation exposure may necessitate spacecraft design concessions and some restriction of mission activities. In this paper we discuss our model calculations of radiation doses in several exo-magnetospheric environments. Specific radiation shielding strategies are discussed. A new calculation of aluminum equivalents of potential spacecraft shielding materials demonstrates the importance of low-atomic-mass species for protection from galactic cosmic radiation.     

Radiation risk estimation and its application to human beings in space.

The number of human beings likely to spend time in space will increase as time goes on. While exposures vary according to missions, orbits, shielding, etc., an average space radiation fluence (ignoring solar flares, radiation belts and anomalous regions in space) in locations close to earth is about 10 rad/year with a quality factor of about 5.5. The potential effects of exposure to these fluences include both non-stochastic effects and stochastic effects (cancer and genetic damage). Non-stochastic effects, damage to the lens of the eye, bone marrow or gonads, can be avoided by keeping radiation limits below threshold values. Stochastic effects imply risk at all levels. The magnitude of these risks has been discussed in a number of reports by the UNSCEAR Committee and the BEIR Committee in the USA during 1970-1980. The uncertainties associated with these risks and information which has become available since the last BEIR report is discussed. In considering reasonable limits for exposure in space, acceptable levels for stochastic risks must be based on appropriate comparisons. In view of the limited term of duty of most space workers, a lifetime limit may be appropriate. This lifetime limit might be comparable in terms of risks with limits for radiation workers on the ground but received at a higher annual rate for a shorter time. These and other approaches are expected to be considered by an NCRP Committee currently examining the problem of space radiation hazards.