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NASA NTRSDate not supplied

Simulation of Radiation-Induced DNA Damage With the Code RITRACKS

INTRODUCTION DNA damage is one of the most physiologically important effects of ionizing radiation. Clustered DNA damage events, like double-strand breaks (DSBs), have the most notable biological consequences. DNA damage types depend on both the track structure of the radiation and the spatial organization of the DNA. High linear energy transfer (LET) charged nuclei, found in galactic cosmic rays (GCR), are known to produce large numbers of complex DNA damage events. The human genome is packaged into chromatin, which can take on locus-dependent and cell type-dependent spatial conformations that correspond to epigenetic states, such as more open, extended structures in transcriptionally active chromatin. These epigenetic differences can affect DNA break patterns in response to ionizing radiation, potentially creating distinct DNA repair and signaling outcomes across the genome in different cells. MATERIAL AND METHODS The code RITRACKS (Relativistic Ion Tracks), which simulates stochastic radiation track structures and radiation chemistry, was used to model damage on isolated and histone-bound DNA by various types of ions and photons. The changes made to the code to perform radiation-induced DNA damage, and simulation results on single nucleosomes are given in our recent paper. In this work, the DNA building capabilities of RITRACKS have been extended to simulate more complex DNA structures build on the coarse-grain simulation framework meso-WLCsim. This code can sample generic chromatin fiber conformation ensembles based on the geometry of nucleosomes and mechanical properties of DNA. Using RITRACKS, we simulated the fragment length distributions (FLD) of irradiated DNA structures built using the chromatin conformations of WLCsim and obtained results representative of those obtained with Radiation-Induced Correlated Cleavage with sequencing (RICC-Seq) experiments [6]. We have also performed Fe ion and photon irradiations of K562, IMR90, BJ and RPE-1 cells at NSRL to experimentally validate results. Sample processing and data analysis are in progress and any available preliminary results will be discussed. DISCUSSION The recent updates in the code RITRACKS allow the calculation of several quantities such as the DNA damage yield and the FLD. This approach can be used to model epigenetic state-specific chromatin structure parameters to leverage the epigenetic state data available for many human cell types to infer relative DNA damage sensitivity among genomic loci.

I Plante↗

NASA NTRS1983

Prochloron research

The purpose was to prepare Prochloron photosynthetic membranes for the isolation of the two major chlorophyll-proteins, the P700-chlorophyll a-protein and the light-harvesting chlorophyll a/b-protein, using SDS-polyacrylamide gel electrophoresis. The prepared proteins (purified) were examined for their cross-reactivity to polyclonal antibodies prepared from higher plant proteins. In addition, material was prepared for electron microscopy, and isolation of the DNA for determination of its general complexity (COT analysis) and similarity to barley chloroplast DNA and Anabaena DNA by using restriction-endonuclease analysis. Kleinschmidt spreads of the DNA were in the electron microscope to identify and measure the extent and size of the circlar DNA.

Lewin, R. A.↗

NASA NTRS1983

Prochloron expedition

The purpose was to prepare Prochloron phototsynthetic membranes for the isolation of the two major chlorophyll-proteins, the p700-chlorophyll a protein and the light harvesting chlorophyll a/b-protein, using SDS-polyacrylamide get electrophoreses. The prepared proteins (purified) were examined for their cross-reactivity to polyclonal antibodies prepared from higher plant proteins. In addition, material was prepared for electron microscopy, and isolation of the DNA for determination of its general complexity (COT analysis) and similarity to barley chloroplast DNA and Anabaena DNA by using restriction-endonuclease analysis Kleinschmidt spreads of the DNA were in the electron microscope to identify and measure the extent and size of the circular DNA.

Alberte, R. S.↗

NASA NTRS1996

Mass Storage and Retrieval at Rome Laboratory

As the speed and power of modern digital computers continues to advance, the demands on secondary mass storage systems grow. In many cases, the limitations of existing mass storage reduce the overall effectiveness of the computing system. Image storage and retrieval is one important area where improved storage technologies are required. Three dimensional optical memories offer the advantage of large data density, on the order of 1 Tb/cm(exp 3), and faster transfer rates because of the parallel nature of optical recording. Such a system allows for the storage of multiple-Gbit sized images, which can be recorded and accessed at reasonable rates. Rome Laboratory is currently investigating several techniques to perform three-dimensional optical storage including holographic recording, two-photon recording, persistent spectral-hole burning, multi-wavelength DNA recording, and the use of bacteriorhodopsin as a recording material. In this paper, the current status of each of these on-going efforts is discussed. In particular, the potential payoffs as well as possible limitations are addressed.

Kann, Joshua L.↗

NASA NTRS1973

Macromolecular fractionation and determination

Biological materials were recovered from other materials ultracentrifugation techniques. Data cover fatty acid synthetase, acetyl-CoA synthetase, ribosomes, DNA, RNA, and AMP.

Chao, F.↗

NASA NTRS2004

Role of shielding in modulating the effects of solar particle events: Monte Carlo calculation of absorbed dose and DNA complex lesions in different organs

Distributions of absorbed dose and DNA clustered damage yields in various organs and tissues following the October 1989 solar particle event (SPE) were calculated by coupling the FLUKA Monte Carlo transport code with two anthropomorphic phantoms (a mathematical model and a voxel model), with the main aim of quantifying the role of the shielding features in modulating organ doses. The phantoms, which were assumed to be in deep space, were inserted into a shielding box of variable thickness and material and were irradiated with the proton spectra of the October 1989 event. Average numbers of DNA lesions per cell in different organs were calculated by adopting a technique already tested in previous works, consisting of integrating into "condensed-history" Monte Carlo transport codes--such as FLUKA--yields of radiobiological damage, either calculated with "event-by-event" track structure simulations, or taken from experimental works available in the literature. More specifically, the yields of "Complex Lesions" (or "CL", defined and calculated as a clustered DNA damage in a previous work) per unit dose and DNA mass (CL Gy-1 Da-1) due to the various beam components, including those derived from nuclear interactions with the shielding and the human body, were integrated in FLUKA. This provided spatial distributions of CL/cell yields in different organs, as well as distributions of absorbed doses. The contributions of primary protons and secondary hadrons were calculated separately, and the simulations were repeated for values of Al shielding thickness ranging between 1 and 20 g/cm2. Slight differences were found between the two phantom types. Skin and eye lenses were found to receive larger doses with respect to internal organs; however, shielding was more effective for skin and lenses. Secondary particles arising from nuclear interactions were found to have a minor role, although their relative contribution was found to be larger for the Complex Lesions than for the absorbed dose, due to their higher LET and thus higher biological effectiveness. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Non-NASA Center↗

NASA NTRS1999

In-Situ Spectrometry of Neutrons

High energy charged particles of extra-galactic, galactic and solar origin collide with spacecraft structures in Earth orbit outside the atmosphere and in interplanetary travel beyond the Earth's magnetosphere. These primaries create a number of secondary particles inside the structures that can produce a significant ionizing radiation environment. This radiation is a threat to long term inhabitants or travelers for space missions and produces an increased risk of cancer and DNA damage. The primary high energy cosmic rays and trapped protons collide with common spacecraft materials such as aluminum and silicon and create secondary particles inside structures that are mostly protons and neutrons. Charged protons are readily detected and instruments are already in existence for this task. Neutrons are electrically neutral and therefore much more difficult to measure and detect. These neutrons are reported to contribute 30-60% of the dose inside space structures and cannot be ignored. Currently there is no compact, portable and real time neutron detector instrumentation available for use inside spacecraft or on planetary surfaces where astronauts will live and work. We propose to design and build a portable, low power and robust neutron spectrometer that will measure the neutron spectrum from 10 KeV to 500 MeV with at least 10% energy resolution in the various energy intervals. This instrument will monitor the existing neutron environment both inside spacecraft structures and on planetary surfaces to determine the safest living areas, warn of high fluxes associated with solar storms and assist the NSBRI Radiation Effects Team in making an accurate assessment of increased cancer risk and DNA damage to astronauts. The instrument uses a highly efficient proportional counter Helium 3 tube at the lowest energy intervals where .equivalent damage factors for tissue are the highest (10 KeV-2 MeV). The Helium 3 tube may be shielded with a cadmium absorber to eliminate the much less damaging, but more prevalent, thermal and epithermal neutrons and to make the structure of the spectrum more accurate in the 20 KeV-2 MeV range; or a pair of tubes, one shielded and one unshielded, can be combined so that the difference in their counts yields the thermal neutron contribution. The spectrometer also uses a 5mm lithium drifted bulk silicon solid state detector in the medium energy range of 2-20 Mev and two standard silicon surface barrier detectors separated by tens of millimeters behind a I cm thick polyethylene moderator in a stack or telescope arrangement for the high energy neutrons (>20 MeV). In the medium and high energy regions equivalent damage factors are lower but hits from one or a small number of neutrons may prove to be important. The silicon detector systems for medium and high energy neutrons will discriminate against charged particles by using a plastic cesium iodide scintillator of an appropriate geometry monitored by a silicon PIN photodiode.

Maurer, Richard H.↗

NASA NTRS2002

Nanotechnology Based Materials and Devices for Health Care

This viewgraph presentation provides information on trends in NASA nanotechnology research and development, and future biotechnological applications for that nanotechnology. The presentation covers nanoelectronics, nanosensors, and nanomaterials, biomimetics, devices and materials for health care, carbon nanotubes, biosensors for astrobiology, solid-state nanopores for DNA sequencing, and protein nanotubes.

Srivastava, Deepaka↗

NASA NTRS1990

Revival of Dobell's "chromidia" hypothesis: chromatin bodies in the amoebomastigote Paratetramitus jugosus

Multiple fission of a mature Paratetramitus jugosus (approx. 10 micrometers long) resulted in the production of many small, roughly spherical (2-7 micrometers in diameter) amoebae. Our observation of live material and examination of over two hundred micrographs lead us to suggest that DNA-containing membrane-bounded chromatin bodies bud amitotically from the nucleus. DAPI-stained bodies of these were observed in the cytoplasm of amoebae, mastigotes, and cysts, and at least some of these chromatin bodies seemed to be released into the medium. This interpretation revives for P. jugosus the "chromatin hypothesis" of Dobell. Our data, consistent with the descriptions of Dobell, Hogue, and Wherry, indicate that encysting amoebae may reproduce by chromidia. Dobell's original chromidia concept was limited to amoebae. Others claimed for it far-reaching consequences: "chromidia" were touted as an explanation for embryogenesis and histogenesis of metazoa. Although there is no evidence for chromidia in animals, outright rejection of Dobell's chromidia hypothesis sensu stricto as an amitotic multiple fission process in amoebae is unjustified.

Non-NASA Center↗

NASA NTRS2002

Abundant raw material for cis-regulatory evolution in humans

Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (<13,000), in part because of an overrepresentation among the former in multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role of microsatellites in gene expression variation may provide a larger store of heritable phenotypic variation, and a more rapid mutational input of such variation, than has been realized. Finally, we outline the distinctive consequences of cis-regulatory variation for the genotype-phenotype relationship, including ubiquitous epistasis and genotype-by-environment interactions, as well as underappreciated modes of pleiotropy and overdominance. Ordinary small-scale mutations contribute to pervasive variation in transcription rates and consequently to patterns of human phenotypic variation.

NASA Discipline Evolutionary Biology↗

NASA NTRS1995

PCR Based Microbial Monitor for Analysis of Recycled Water Aboard the ISSA: Issues and Prospects

The monitoring of spacecraft life support systems for the presence of health threatening microorganisms is paramount for crew well being and successful completion of missions. Development of technology to monitor spacecraft recycled water based on detection and identification of the genetic material of contaminating microorganisms and viruses would be a substantial improvement over current NASA plans to monitor recycled water samples that call for the use of conventional microbiology techniques which are slow, insensitive, and labor intensive. The union of the molecular biology techniques of DNA probe hybridization and polymerase chain reaction (PCR) offers a powerful method for the detection, identification, and quantification of microorganisms and viruses. This technology is theoretically capable of assaying samples in as little as two hours with specificity and sensitivity unmatched by any other method. A major advance in probe-hybridization/PCR has come about in a technology called TaqMan(TM), which was invented by Perkin Elmer. Instrumentation using TaqMan concepts is evolving towards devices that could meet NASA's needs of size, low power use, and simplicity of operation. The chemistry and molecular biology needed to utilize these probe-hybridization/PCR instruments must evolve in parallel with the hardware. The following issues of chemistry and biology must be addressed in developing a monitor: Early in the development of a PCR-based microbial monitor it will be necessary to decide how many and which organisms does the system need the capacity to detect. We propose a set of 17 different tests that would detect groups of bacteria and fungus, as well as specific eukaryotic parasites and viruses; In order to use the great sensitivity of PCR it will be necessary to concentrate water samples using filtration. If a lower limit of detection of 1 microorganism per 100 ml is required then the microbes in a 100 ml sample must be concentrated into a volume that can be added to a PCR assay; There are not likely to be contaminants in ISSA recycled water that would inhibit PCR resulting in false-negative results; The TaqMan PCR product detection system is the most promising method for developing a rapid, highly automated gene-based microbial monitoring system. The method is inherently quantitative. NASA and other government agencies have invested in other technologies that, although potentially could lead to revolutionary advances, are not likely to mature in the next 5 years into working systems; PCR-based methods cannot distinguish between DNA or RNA of a viable microorganism and that of a non-viable organism. This may or may not be an important issue with reclaimed water on the ISSA. The recycling system probably damages the capacity of the genetic material of any bacteria or viruses killed during processing to serve as a template in a PCR desinged to amplify a large segment of DNA (less than 650 base pairs). If necessary, vital dye staining could be used in addition to PCR, to enumerate the viable cells in a water sample; The quality control methods have been developed to insure that PCR's are working properly, and that reactions are not contaminated with PCR carryover products which could lead to the generation of false-positive results; and The sequences of the small rRNA subunit gene for a large number of microorganisms are known, and they consititue the best database for rational development of the oligonucleotide reagents that give PCR its great specificity. From those gene sequences, sets of oligonucleotide primers for PCR and Taqman detection that could be used in a NASA microbial monitor were constructed using computer based methods. In addition to space utilization, a microbial monitior will have tremendous terrestrial applications. Analysis of patient samples for microbial pathogens, testing industrial effluent for biofouling bacteria, and detection biological warfare agents on the battlefield are but a few of the diverse potential uses for this technology. Once fully developed, gene-based microbial monitors will become the fundamental tool in every lab that tests for microbial contaminants, and serve as a powerful weapon in mankind's war with the germ world.

Cassell, Gail H.↗

NASA NTRS2013

Galactic Cosmic Ray Event-Based Risk Model (GERM) Code

This software describes the transport and energy deposition of the passage of galactic cosmic rays in astronaut tissues during space travel, or heavy ion beams in patients in cancer therapy. Space radiation risk is a probability distribution, and time-dependent biological events must be accounted for physical description of space radiation transport in tissues and cells. A stochastic model can calculate the probability density directly without unverified assumptions about shape of probability density function. The prior art of transport codes calculates the average flux and dose of particles behind spacecraft and tissue shielding. Because of the signaling times for activation and relaxation in the cell and tissue, transport code must describe temporal and microspatial density of functions to correlate DNA and oxidative damage with non-targeted effects of signals, bystander, etc. These are absolutely ignored or impossible in the prior art. The GERM code provides scientists data interpretation of experiments; modeling of beam line, shielding of target samples, and sample holders; and estimation of basic physical and biological outputs of their experiments. For mono-energetic ion beams, basic physical and biological properties are calculated for a selected ion type, such as kinetic energy, mass, charge number, absorbed dose, or fluence. Evaluated quantities are linear energy transfer (LET), range (R), absorption and fragmentation cross-sections, and the probability of nuclear interactions after 1 or 5 cm of water equivalent material. In addition, a set of biophysical properties is evaluated, such as the Poisson distribution for a specified cellular area, cell survival curves, and DNA damage yields per cell. Also, the GERM code calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle in a selected material. The GERM code makes the numerical estimates of basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at the NASA Space Radiation Laboratory (NSRL) for the purpose of simulating space radiation biological effects. In the first option, properties of monoenergetic beams are treated. In the second option, the transport of beams in different materials is treated. Similar biophysical properties as in the first option are evaluated for the primary ion and its secondary particles. Additional properties related to the nuclear fragmentation of the beam are evaluated. The GERM code is a computationally efficient Monte-Carlo heavy-ion-beam model. It includes accurate models of LET, range, residual energy, and straggling, and the quantum multiple scattering fragmentation (QMSGRG) nuclear database.

Cucinotta, Francis A.↗

NASA NTRSDate not supplied

Investigation of Prophage Regions of Bacterial Strains Isolated from the International Space Station (ISS)

Space flight agencies are planning missions back to the Moon and to Mars. When sending humans into space, it is impossible to separate them from microorganisms, either in their associated microbiome or in the spacecraft environment, which are modified through the movement of genetic material. Bacteriophages, small viruses that invade and replicate within bacterial cells, play a central role in the genetic composition and evolution of microorganisms. Lysogenic bacteriophages can insert themselves into the DNA of their bacterial hosts, forming prophage regions, which can also transfer genes from previous hosts. Thus, we aimed to identify and classify all prophages from twelve bacterial species cultured from the International Space Station (ISS) from 2017 to 2018. We determined representative bacterial strains for each species, whose genomes were analyzed to identify prophage regions. Complete prophages were identified through database searches and the number of prophage regions were compared to terrestrial analogs. Additionally, prophage region and genome sizes were compared for each species, identifying the percentage of bacteriophage DNA in each genome. We determined that the prophage-susceptible bacterial species isolated from the ISS had a higher number of prophage regions when compared to terrestrial analogs, as well as having a larger percentage of their genomes made up of prophage material. Of the eighteen complete prophages identified, 72.2% were of family Siphoviridae and 27.8% were of family Myoviridae. Only one of the prophages had a BLAST similarity over 80%, suggesting that the remainder of prophages are novel species. These results imply that there is a higher rate of prophage transduction and lysogeny during spaceflight, and that the prophages present are novel.

Phage↗

NASA NTRS2001

Microbial Contamination of Allende and Murchison Carbonaceous Chondrites; Developing a Protocol for Life Detection in Extraterrestrial Materials Using Biotechnology

The arguments used to refute the McKay et al., (1996) hypothesis of possible Martian life in ALH84001 failed to use contamination of the meteorite as a source. This has worrying implications for our ability to detect terrestrial microbiota in meteorites and therefore any potential extraterrestrial biosignatures in both meteorites and possible returned samples. We report on imaging and microbial culturing of both Allende and Murchison carbonaceous chondrites and on the use of molecular biology techniques on a sample of Allende. Contaminating fungi and bacteria were observed (in the case of Murchison) and cultured from both meteorites. DNA was successfully extracted and subsequent PCR showed the presence of both bacterial and fungal DNA although no Archaea were detected. These results show that it is possible to use molecular biological techniques on very small quantities (300 mg) of extraterrestrial material.

Steele, A.↗

NASA NTRS2011

The Analysis of the Patterns of Radiation-Induced DNA Damage Foci by a Stochastic Monte Carlo Model of DNA Double Strand Breaks Induction by Heavy Ions and Image Segmentation Software

To create a generalized mechanistic model of DNA damage in human cells that will generate analytical and image data corresponding to experimentally observed DNA damage foci and will help to improve the experimental foci yields by simulating spatial foci patterns and resolving problems with quantitative image analysis. Material and Methods: The analysis of patterns of RIFs (radiation-induced foci) produced by low- and high-LET (linear energy transfer) radiation was conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Some data analysis was done with the help of image segmentation software that identifies individual classes of RIFs and colocolized RIFs, which is of importance to some experimental assays that assign DNA damage a dual phosphorescent signal. Results: The model predicts the spatial and genomic distributions of DNA DSBs (double strand breaks) and associated RIFs in a human cell nucleus for a particular dose of either low- or high-LET radiation. We used the model to do analyses for different irradiation scenarios. In the beam-parallel-to-the-disk-of-a-flattened-nucleus scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular-beam scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. In another analysis, our image segmentaiton software determined foci yields directly from images with single-class or colocolized foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantization of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiments using proteins that detect DNA damage. An automated image segmentaiton software can prove useful in a faster and more precise object counting for colocolized foci images.

Ponomarev, Artem↗

NASA NTRS1991

Fiber optic-based biosensor

The NRL fiber optic biosensor is a device which measures the formation of a fluorescent complex at the surface of an optical fiber. Antibodies and DNA binding proteins provide the mechanism for recognizing an analyze and immobilizing a fluorescent complex on the fiber surface. The fiber optic biosensor is fast, sensitive, and permits analysis of hazardous materials remote from the instrumentation. The fiber optic biosensor is described in terms of the device configuration, chemistry for protein immobilization, and assay development. A lab version is being used for assay development and performance characterization while a portable device is under development. Antibodies coated on the fiber are stable for up to two years of storage prior to use. The fiber optic biosensor was used to measure concentration of toxins in the parts per billion (ng/ml) range in under a minute. Immunoassays for small molecules and whole bacteria are under development. Assays using DNA probes as the detection element can also be used with the fiber optic sensor, which is currently being developed to detect biological warfare agents, explosives, pathogens, and toxic materials which pollute the environment.

Ligler, Frances S.↗

NASA NTRS1995

The Relative Reactivity of Deoxyribose and Ribose: Did DNA Come Before RNA?

If it is assumed that there was a precursor to the ribose-phosphate backbone of RNA in the preRNA world (such as peptide nucleic acid), then the entry of various sugars into the genetic material may be related to the stability and non-enzymatic reactivity of the aldose. The rate of decomposition of 2-deoxyribose has been determined to be 1/3 that of ribose. In addition we have measured the amount of free aldehyde by H-1 and C-13 NMR and find that it has approximately 0.15% free aldehyde compared to 0.05% for ribose at 25 C. This suggests that deoxyribose would be significantly more reactive with early bases in the absence of enzymes. This is confirmed by urazole and deoxyribose reacting to form the deoxynucleoside 45 times faster as 25 C than urazole reacts with ribose to form the Ribonucleoside. Urazole is a potential precursor of uracil and is a plausible prebiotic compound which reacts with aldoses to form nucleosides. Thus the non-enzymatic reactivity of deoxyribose would favor its early use over ribose until enzymes could change the relative reactivities. Most of the reasons that RNA is presumed to have come before DNA are extrapolations back from contemporary metabolism (e.g. the abundance of ribose based coenzymes, the biosynthesis of histidine, deoxyribonucleotides are synthesized from ribonucleotides, etc.). It is very difficult to reconstruct biochemical pathways much before the last common ancestor, and it is even more difficult to do more than guess at the biochemistry of very early self-replicating systems. Thus we believe that these reasons are not compelling and that the non-enzymatic chemistry may be more important than enzymatic pathways for constructing the earliest of biochemical pathways. While the RNA world has been discussed at great length, there has not been an exploration of the transition out of the RNA world. We have constructed many possible schemes of genetic takeover events from preRNA to modern DNA, RNA, protein system which could generate the RNA metabolic fossils we see today.

Dworkin, Jason P.↗

NASA NTRS2010

Monte-Carlo Simulation of Radiation Track Structure and Calculation of Dose Deposition in Nanovolumes

INTRODUCTION: The radiation track structure is of crucial importance to understand radiation damage to molecules and subsequent biological effects. Of a particular importance in radiobiology is the induction of double-strand breaks (DSBs) by ionizing radiation, which are caused by clusters of lesions in DNA, and oxidative damage to cellular constituents leading to aberrant signaling cascades. DSB can be visualized within cell nuclei with gamma-H2AX experiments. MATERIAL AND METHODS: In DSB induction models, the DSB probability is usually calculated by the local dose obtained from a radial dose profile of HZE tracks. In this work, the local dose imparted by HZE ions is calculated directly from the 3D Monte-Carlo simulation code RITRACKS. A cubic volume of 5 micron edge (Figure 1) is irradiated by a (Fe26+)-56 ion of 1 GeV/amu (LET approx.150 keV/micron) and by a fluence of 450 H+ ions, 300 MeV/amu (LET approx. 0.3 keV/micron). In both cases, the dose deposited in the volume is approx.1 Gy. The dose is then calculated into each 3D pixels (voxels) of 20 nm edge and visualized in 3D. RESULTS AND DISCUSSION: The dose is deposited uniformly in the volume by the H+ ions. The voxels which receive a high dose (orange) corresponds to electron track ends. The dose is deposited differently by the 56Fe26+ ion. Very high dose (red) is deposited in voxels with direct ion traversal. Voxels with electron track ends (orange) are also found distributed around the path of the track. In both cases, the appearance of the dose distribution looks very similar to DSBs seen in gammaH2AX experiments, particularly when the visualization threshold is applied. CONCLUSION: The refinement of the dose calculation to the nanometer scale has revealed important differences in the energy deposition between high- and low-LET ions. Voxels of very high dose are only found in the path of high-LET ions. Interestingly, experiments have shown that DSB induced by high-LET radiation are more difficult to repair. Therefore, this new approach may be useful to understand the nature of DSB and oxidative damage induced by ionizing radiation.

Plante, I.↗