Induction of high grade astrocytoma (HGA) by protons: molecular mechanisms and RBE considerations.

Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique "toxic" property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.     

RBE for non-stochastic effects.

Evidence is reviewed concerning the variation of RBE values of high-LET radiations for non-stochastic effects, generally impairment of tissue integrity and function. The RBE values are dependent on the type of radiation, the type of tissue effect and the dose rate or fractionation schedule. RBE values depend strongly on the effect considered, with high values for late effects in lung, kidney and central nervous system. RBE values generally increase with decreasing dose rate or dose per fraction. Maximum values can be derived by extrapolation on the basis of a radiobiological model. These values are denoted RBEm to distinguish them from RBEM derived for stochastic effects, e.g. carcinogenesis. Values of RBEm are generally in the range of 2 to 10 and are considerably smaller by a factor of 2 to 5 than values of RBEM for various types of stochastic effects. RBE values for effects from actual exposures to mixtures of high-LET and low-LET radiations can be derived by considering the doses received and the tissue at risk. Applications of RBEm values will yield estimates of maximum values of equivalent doses and these should only be applied for planning medical interventions if the contribution from high-LET radiation is small. The selection of Q values for radiation protection is mostly based on RBE--values and the application of Q values in cases where non-stochastic effects are important might therefore result in an overestimate of the risks of exposure.     

Experimental models for cellular radiation targets: LET, RBE and radioprotectors.

The topics of this presentation are: a brief review of the early research, the ideas it stimulated and the ways they are used in current efforts to explain cellular radiosensitivity; an analysis of the strengths and weaknesses of two experimental models used in vitro for simulating the induction of double strand breaks (DSB) and single strand breaks (SSB) in situ. Note that when alkali is used to denature cellular DNA for the determination of strand breaks, both overt SSB and the SSB that result from DSB in the denaturation process are recorded as total strand breaks (TSB). All information is taken from published literature.     

Repair of DNA double-strand breaks and its effect on RBE.

DNA double-strand breaks (DSB) are induced linearly with absorbed dose both for sparsely and densely ionizing radiations. By enzymatic repair the linear relationship between the number of DSB and absorbed dose is converted into a non linear one. Furthermore, the RBE-values of high LET radiations for residual DSB increase with increasing amount of DSB repair especially in the low dose range. Unrepaired and/or misrepaired DSB are supposed to be responsible for chromosomal aberrations, cell killing, oncogenic cell transformation and gene mutation. At low doses, for these endpoints much higher RBE-values than those for initial DSB are observed. However, with increasing doses the RBE-values for these endpoints approach those for initial DSB. These observations are likely to be interpreted using the following two parameters of the energy deposition structure: 1. The distribution of clusters with respect to their size at the nm-scale and to the number of ionizations per cluster (cluster distribution). 2. The distribution of distances between clusters of definite size and with definite number of ionizations (distance distribution of clusters). For the induction of DSB solely the ionization density in clusters of nm-dimensions (i.e. the cluster distribution) is important. For unrepaired or misrepaired DSB (responsible for chromosome aberrations, cell killing, oncogenic cell transformation and gene mutation) both the cluster distribution and the distance distribution of clusters are relevant. At low doses the distance distribution of clusters along a single particle track determines the RBE-value. However, with increasing dose the distribution of clusters produced by all particles traversing the cell nucleus becomes increasingly determinant. Here, solely the cluster distribution is important as it is the case for the induction of DSB.     

Monte Carlo track structure studies of energy deposition and calculation of initial DSB and RBE.

Estimation of exposure due to environmental and other sources of radiations of high-LET and low-LET is of interest in radiobiology and radiation protection for risk assessment. To account for the differences in effectiveness of different types of radiations various parameters have been used. However, the relative inadequacy of the commonly used parameters, including dose, fluence, linear energy transfer, lineal energy, specific energy and quality factor, has been made manifest by the biological importance of the microscopic track structure and primary modes of interaction. Monte Carlo track structure simulations have been used to calculate the frequency of energy deposition by radiations of high- and low-LET in target sizes similar to DNA and higher order genomic structure. Tracks of monoenergetic heavy ions and electrons were constructed by following the molecular interaction-by-interaction histories of the particles down to 10 eV. Subsequently, geometrical models of these assumed biological targets were randomly exposed to the radiation tracks and the frequency of energy depositions obtained were normalized to unit dose in unit density liquid water (l0(3) kg m-3). From these data and a more sophisticated model of the DNA, absolute yields of both single- and double-strand breaks expressed in number of breaks per dalton per Gray were obtained and compared with the measured yields. The relative biological effectiveness (RBE) for energy depositions in cylindrical targets has been calculated using 100 keV electrons as the reference radiation assuming the electron track-ends contribution is similar to that in 250 kV X-ray or Co60 gamma-ray irradiations.     

Properties of traveling atmospheric disturbances (TADs) inferred from CHAMP accelerometer observations

Densities derived from accelerometer measurements on the CHAMP satellite near 400 km are used to statistically establish characteristics of large-scale (>1000 km) traveling atmospheric disturbances (TADs). Only TADs that at least propagate from the auroral zone to the equator are analyzed here, and a total of 21 identifiable events are found over the years 2001–2007. The average speed of all TADs, regardless of local time, is 646 ± 122 ms⁻¹. The average speeds on the dayside and nightside are 595 ± 127 ms⁻¹ and 685 ± 106 ms⁻¹, respectively, i.e., the speed appears to be 10% higher on average on the nightside. On six occasions TADs were only detected on the night side; however, TADs on the dayside often appear more distinctly in the data. Moreover, contrary to some theoretical expectations, dayside TADs do not dissipate more readily than night side TADs, although much less are detected between 8–20 solar local time. No clear dependence of TAD amplitude or phase speed with respect to Kp, or rate of increase of Kp, is found.     

The latitude-energy dispersion of precipitating ions inferred from the Intercosmos-Bulgaria-1300 satellite data

The Intercosmos-Bulgaria-1300 (ICB-1300) data are used to study the features of the 0.4–15.0 keV precipitating ion spectrum in auroral regions. The ion spectra recorded during disturbed periods exhibit monochromatic peaks at different energies, with lower energies being shifted to lower invariant latitudes. The results obtained are interpreted in terms of the hypothesis of ion acceleration in the inverted-V regions and their subsequent drift in the crossed electric and magnetic fields when moving to conjugate hemisphere.     

Neoplastic cell transformation by high-LET radiation: molecular mechanisms.

Experimental data on molecular mechanisms are essential for understanding the bioeffects of radiation and for developing biophysical models, which can help in determining the shape of dose-response curves at very low doses, e.g., doses less than 1 cGy. Although it has been shown that ionizing radiation can cause neoplastic cell transformation directly, that high-LET heavy ions in general can be more effective than photons in transforming cells, and that the radiogenic cell transformation is a multi-step process [correction of processes], we know very little about the molecular nature of lesions important for cell transformation, the relationship between lethal and transformational damages, and the evolution of initial damages into final chromosomal aberrations which alter the growth control of cells. Using cultured mouse embryo cells (C3H10T1/2) as a model system, we have collected quantitative data on dose-response curves for heavy ions with various charges and energies. An analysis of these quantitative data suggested that two DNA breaks formed within 80 angstroms may cause cell transformation and that two DNA breaks formed within 20 angstroms may be lethal. Through studies with restriction enzymes which produce DNA damages at specific sites, we have found that DNA double strand breaks, including both blunt- and cohesive-ended breaks, can cause cell transformation in vitro. These results indicate that DNA double strand breaks can be important primary lesions for radiogenic cell transformation and that blunt-ended double strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship is similar for HGPRT gene mutation, chromosomal deletion, and cell transformation, suggesting common lesions may be involved in these radiation effects. The high RBE of high-LET radiation for cell killing and neoplastic cell transformation is most likely related to its effectiveness in producing DNA double strand breaks in mammalian cells. At present the role of oncogenes in radiation cell transformation is unclear.     

Airglow OH emission height inferred from the OH temperature and meteor trail diffusion coefficient

Simultaneous observations of the airglow OH(6,2) band rotational temperature, TOH, and meteor trail ambipolar diffusion coefficient, D, were carried out at Shigaraki (35°N, 136°E), during PSMOS 2003 Campaign, January 28 to February 8, 2003. The OH emission height was estimated by cross correlation analysis of the TOH and D nocturnal variations. A good correlation between TOH and D was obtained at 85 km of altitude. From the nocturnal variations of TOH and D, it is found that the OH emission peak height varied from 88 km before the midnight to 84 km in the early morning. The height variation could be caused by an atmospheric tidal effect in the emission height.     

Putative graviperception mechanisms of protists.

Many (if not all) free-living cells use the gravity vector for their spatial orientation (gravitaxis). Additional responses may include gravikinesis as well as changes in morphological and physiological parameters. Though using essentially different modes of locomotion, ameboid and ciliated cells seem to rely on common fundamental graviperception mechanisms. Uniquely in the ciliate family Loxodidae a specialized intracellular gravireceptor organelle has been developed, whereas in all other cells common cell structures seem to be responsible for gravisensing. Changes in direction or magnitude of acceleration (from 0 to 5 g) as well as experiments in density-adjusted media strongly indicate that either the whole cytoplasm or dense organelles like nuclei act as statoliths and open directly or via cytoskeletal elements mechano-sensitive ion channels in the cell membrane. A recent spaceflight experiment (S/MM-06) demonstrated that prolonged (9 d) actual weightlessness did not affect the ability of Loxodes to respond to acceleration stimuli. However, prolonged cooling (> or = l4 d, 4-10 degrees C) destroyed the ability for gravitactic orientation of Paramecium. This may reflect a profound effect either on the gravireceptor itself or on the gravity-signal processing. In gravity signalling the ubiquitous second messenger cAMP may be involved in acceleration-stimulus transduction.     

Chromosome aberrations as biomarkers of radiation exposure: modelling basic mechanisms.

The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).     

Radioprotection of DNA by biochemical mechanisms.

The title of this presentation should be understood as having two facets: the preservation of genetic information and function by protecting the DNA from the deleterious effects of radiation by reducing the degree of damage, is one important task. Yet another, which may be as important, is the utilization of biochemical entities whose function is to repair damages which have already been formed in DNA, thus enhancing the protection of living cells.     

Chairman's introduction: mechanisms, models and experiments in space radiation research.

Radiation risk estimate in space is a moral obligation and a scientific challenge requiring the combined efforts of physicists and biologists. This introductory paper presents some thoughts about problems to be solved and the possible directions of research. It stresses the necessity of cooperation across disciplines and the combination of space and ground based investigations.     

Height of shock formation in the solar corona inferred from observations of type II radio bursts and coronal mass ejections

Employing coronagraphic and EUV observations close to the solar surface made by the Solar Terrestrial Relations Observatory (STEREO) mission, we determined the heliocentric distance of coronal mass ejections (CMEs) at the starting time of associated metric type II bursts. We used the wave diameter and leading edge methods and measured the CME heights for a set of 32 metric type II bursts from solar cycle 24. We minimized the projection effects by making the measurements from a view that is roughly orthogonal to the direction of the ejection. We also chose image frames close to the onset times of the type II bursts, so no extrapolation was necessary. We found that the CMEs were located in the heliocentric distance range from 1.20 to 1.93 solar radii (Rs), with mean and median values of 1.43 and 1.38 Rs, respectively. We conclusively find that the shock formation can occur at heights substantially below 1.5 Rs. In a few cases, the CME height at type II onset was close to 2 Rs. In these cases, the starting frequency of the type II bursts was very low, in the range 25–40 MHz, which confirms that the shock can also form at larger heights. The starting frequencies of metric type II bursts have a weak correlation with the measured CME/shock heights and are consistent with the rapid decline of density with height in the inner corona.     

Possible mechanisms of plant cell wall changes at microgravity.

Space and clinostatic experiments revealed that changes of plant cell wall structure and its function depend on type of tissue and duration of influence. It was shown that clinostat conditions reproduce the part of weightlessness biological effects. It is established that various responses of wall structural-metabolic organization occur at microgravity: changes of cell walls ultrastructure and organelles structure; decrease of synthesis of primary plant cell wall; rearrangements of polysaccharides content. It is shown that mechanisms of plant cell wall changes at microgravity are connected with decrease of cellulose crystallization, activation of pectolytic enzymes and rearrangement of calcium balance of apoplast and cytoplasm.     

Biochemical mechanisms and clusters of damage for high-LET radiation.

Using mechanisms of indirect and direct radiation, a generalized theory has been developed to account for strand break yields by high-LET particles. The major assumptions of this theory are: (i) damage at deoxyribose sites results primarily in strand break formation and (2) damage to bases leads to a variety of base alterations. Results of the present theory compare well with cellular data without enzymatic repair. As an extension of this theory, we show that damage clusters are formed near each double strand break for high-LET radiation only. For 10 MeV/n (LET = 450 keV/micrometer) neon ions, the results show that on average there are approximately 3 additional breaks and approximately 3 damaged bases formed near each double strand break. For 100 MeV/n helium ions (LET = 3 keV/micrometer), less than 1% of the strand breaks have additional damage within 10 base pairs.     

Nighttime thermospheric meridional neutral winds inferred from ionospheric h′F and hpF2 data

Nighttime thermospheric meridional winds aligned to the magnetic meridian have been inferred using h′F and hpF2 ionosonde data taken from two equatorial stations, Manaus (2.9°S, 60.0°W, dip latitude 6.0°N) and Palmas (10.17°S, 48.2°W, dip latitude 6.2°S), and one low-latitude station, Sao Jose dos Campos (23.21°S, 45.86°W, dip latitude 17.26°S), during geomagnetic quiet days of August and September, 2002. Using an extension of the ionospheric servo model and a simple formulation of the diffusive vertical drift velocity, the magnetic meridional component of the thermospheric neutral winds is inferred, respectively, at the peak (hpF2) and at the base (h′F) heights of the F region over Sao Jose dos Campos. An approach has been included in the models to derive the effects of the electrodynamic drift over Sao Jose dos Campos from the time derivative of hpF2 and h′F observed at the equatorial stations. The magnetic meridional winds inferred from the two methods, for the months of August and September, are compared with winds calculated using the HWM-90 model and with measurements from Fabry–Perot technique. The results show varying agreements and disagreements. Meridional winds calculated from hpF2 ionospheric data (servo model) may produce errors of about 59 m/s, whereas the method calculated from the F-region base height (h′F) ionospheric data gives errors of about 69 m/s during the occurrence of equatorial spread-F.     

An introduction to gravity perception in plants and fungi--a multiplicity of mechanisms.

The origin and subsequent evolution of life on Earth has taken place within an environment of which a 1g gravitational force is a part. Thus, all living organisms accommodate this variable in their structure and function. Evolution has also selected mechanisms to sense gravity which, in consequence, give particular orientations to living process. It is anticipated that the higher the evolutionary status of an organism, the greater the chance that it will possess multiple mechanisms of gravisensing because evolution discards nothing that assists fitness, but only adds to existing processes. A multiplicity of mechanisms permits gravity to participate in a wide range of developmental programmes, such as taxes, morphisms and tropisms, through the action of different sensors and distinct transduction/response pathways.