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Wu, H.

Publications and source records attributed to Wu, H..

At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS2007

M-Band Analysis of Chromosome Aberrations in Human Epithelial Cells Induced By Low- and High-Let Radiations

Energetic primary and secondary particles pose a health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET radiation is much more effective than low-LET radiation in the induction of various biological effects, including cell inactivation, genetic mutations, cataracts and cancer. Most of these biological endpoints are closely correlated to chromosomal damage, which can be utilized as a biomarker for radiation insult. In this study, human epithelial cells were exposed in vitro to gamma rays, 1 GeV/nucleon Fe ions and secondary neutrons whose spectrum is similar to that measured inside the Space Station. Chromosomes were condensed using a premature chromosome condensation technique and chromosome aberrations were analyzed with the multi-color banding (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of both interchromosomal (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Results of the study confirmed the observation of higher incidence of inversions for high-LET irradiation. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. Half of the inversions observed in the low-LET irradiated samples were accompanied by other types of intrachromosome aberrations, but few inversions were accompanied by interchromosome aberrations. In contrast, Fe ions induced a significant fraction of inversions that involved complex rearrangements of both the inter- and intrachromosome exchanges.

Hada, M.↗
NASA NTRS2007

M-BAND Analysis of Chromosome Aberration In Human Epithelial Cells exposed to Gamma-ray and Secondary Neutrons of Low Dose Rate

High-energy secondary neutrons, produced by the interaction of galactic cosmic rays with the atmosphere, spacecraft structure and planetary surfaces, contribute to a significant fraction to the dose equivalent in crew members and passengers during commercial aviation travel, and astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility's "30L" beam line is known to generate neutrons that simulate the secondary neutron spectrum of the Earth's atmosphere at high altitude. The neutron spectrum is also similar to that measured onboard spacecraft like the MIR and the International Space Station (ISS). To evaluate the biological damage, we exposed human epithelial cells in vitro to the LANSCE neutron beams at an entrance dose rate of 2.5 cGy/hr or gamma-ray at 1.7cGy/hr, and assessed the induction of chromosome aberrations that were identified with mBAND. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of inter-chromosomal aberrations (translocation to unpainted chromosomes) and intra-chromosomal aberrations (inversions and deletions within a single painted chromosome). Compared to our previous results for gamma-rays and 600 MeV/nucleon Fe ions of high dose rate, the neutron data showed a higher frequency of chromosome aberrations. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. The low dose rate gamma-rays induced a lower frequency of chromosome aberrations than high dose rate gamma-rays, but the inversion spectrum was similar for the same cytotoxic effect. The distribution of damage sites on chromosome 3 for different radiation types will also be discussed.

Hada, M.↗
NASA NTRS2007

Break Point Distribution on Chromosome 3 of Human Epithelial Cells exposed to Gamma Rays, Neutrons and Fe Ions

Most of the reported studies of break point distribution on the damaged chromosomes from radiation exposure were carried out with the G-banding technique or determined based on the relative length of the broken chromosomal fragments. However, these techniques lack the accuracy in comparison with the later developed multicolor banding in situ hybridization (mBAND) technique that is generally used for analysis of intrachromosomal aberrations such as inversions. Using mBAND, we studied chromosome aberrations in human epithelial cells exposed in vitro to both low or high dose rate gamma rays in Houston, low dose rate secondary neutrons at Los Alamos National Laboratory and high dose rate 600 MeV/u Fe ions at NASA Space Radiation Laboratory. Detailed analysis of the inversion type revealed that all of the three radiation types induced a low incidence of simple inversions. Half of the inversions observed after neutron or Fe ion exposure, and the majority of inversions in gamma-irradiated samples were accompanied by other types of intrachromosomal aberrations. In addition, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosome exchanges. We further compared the distribution of break point on chromosome 3 for the three radiation types. The break points were found to be randomly distributed on chromosome 3 after neutrons or Fe ions exposure, whereas non-random distribution with clustering break points was observed for gamma-rays. The break point distribution may serve as a potential fingerprint of high-LET radiation exposure.

Hada, M.↗
NASA NTRS2006

Inter- and Intra-Chromosomal Aberrations in Human Cells Exposed in vitro to High and Low LET Radiations

Energetic heavy ions pose a health risk to astronauts in extended ISS and future Mars missions. High-LET heavy ions are particularly effective in causing various biological effects including cell inactivation, genetic mutations and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied chromosome aberrations in human lymphocytes and fibroblasts induced by both low- and high-LET radiation using FISH and multicolor fluorescence in situ hybridization (mFISH) techniques. In this study, we exposed human epithelial cells in vitro to gamma rays and energetic particles of varying types and energies and dose rates, and analyzed chromosomal damages using the multicolor banding in situ hybridization (mBAND) procedure. Confluent human epithelial cells (CH184B5F5/M10) were exposed to energetic heavy ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory, high energy neutron at the Los Alamos Nuclear Science Center (LANSCE) or Cs-137-gamma radiation source at the University of Texas, MD Anderson Cancer Center. After colcemid and Calyculin A treatment, cells were fixed and painted with XCyte3 mBAND kit (MetaSystems) and chromosome aberrations were analyzed with mBAND analysis system (MetaSystems). With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). The results of the mBAND study showed a higher ratio of inversion involved with interchromosomal exchange in heavy ions compared to -ray irradiation. Analysis of chromosome aberrations using mBAND has the potential to provide useful information on human cell response to space-like radiation.

Hada, M.↗
NASA NTRS2006

Induction of Micronuclei in Human Fibroblasts across the Bragg Curve of Energetic Si and Fe Ions

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal since biological effects are influenced by the track structure of both primary and secondary particles. Therefore, the biological Bragg curve is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. We studied micronuclei (MN) induction across the Bragg curve of Si and Fe ions at incident energies of 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono- to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak are likely to go through reproduction death.

Wu, H.↗
NASA NTRS2005

Inter- and Intra-Chromosomal Aberrations in Human Cells Exposed in vitro to Space-like Radiations

Energetic heavy ions pose a great health risk to astronauts in extended ISS and future exploration missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied chromosome aberrations in human lymphocytes and fibroblasts induced by both low- and high-LET radiation using FISH and multicolor fluorescence in situ hybridization (mFISH) techniques. In this study, we exposed human cells in vitro to gamma rays and energetic particles of varying types and energies and dose rates, and analyzed chromosomal damages using the multicolor banding in situ hybridization (mBAND) procedure. Confluent human epithelial cells and lymphocytes were exposed to energetic heavy ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory (Upton, NY) or Cs-137 gamma radiation source at the Baylor College (Houston, TX). After colcemid and Calyculin A treatment, cells were fixed and painted with XCyte3 mBAND kit (MetaSystems) and chromosome aberrations were analyzed with mBAND analysis system (MetaSystems). With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). The possible relationship between the frequency of inter- and intra-chromosomal exchanges and the track structure of radiation is discussed. The work was supported by the NASA Space Radiation Health Program.

Hada, Megumi↗
NASA NTRS2005

In Vitro Experimental Model to Investigate the Biological Effects across the Bragg Curve of High-LET Radiation

The space environment consists of a varying field of radiation particles including high energy ions, with a spacecrafts shielding material providing the only major protection to astronauts from harmful exposure. Unlike lowLET gamma or Xrays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak and the correlating spatial dose distribution identified as the Bragg curve. The Bragg curve does not necessarily represent the biological damage along the particle traversal since biological effects are influenced by the track structure of both primary and secondary particles. Therefore, the biological Bragg curve is dependent of the energy and the type of the primary particle, and may vary for different biological endpoints. Here we describe a unique irradiation geometry and experimental system to measure the biological response across the Bragg curve in one consistent biological sample. Polyethylene shielding was used to achieve a Bragg curve distribution with the beam geometry parallel to a monolayer of fibroblast cells. We present data that highlights the differential formation of DNA double strand breaks (DSBs) and chromosomal deletions across the Bragg curve in human fibroblasts irradiated with 600 MeV/nucleon iron ion beams. Qualitative analyses of gammaH2AX fluorescence, a known marker of DSBs, indicated potentially increased clustering of DNA damage before the Bragg peak, enhanced homogenous distribution at the peak, and provided visual evidence of high linear energy transfer (LET) particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. A biological response curve generated for micronuclei induction across the Bragg curve for 600 MeV/n Fe ions did not reveal an increase in the yield of micronuclei at the Bragg peak location. Assessment of such biological parameters employing the described in vitro experimental system may provide improved platforms to measure a number of biological consequences of shielding materials across the Bragg curve for high charge and energy (HZE) ions.

Desai, N.↗
NASA NTRS2005

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cucinotta, F. A.↗
NASA NTRS2004

Simultaneous measurement of multiple radiation-induced protein expression profiles using the Luminex(TM) system

Space flight results in the exposure of astronauts to a mixed field of radiation composed of energetic particles of varying energies, and biological indicators of space radiation exposure provides a better understanding of the associated long-term health risks. Current methods of biodosimetry have employed the use of cytogenetic analysis for biodosimetry, and more recently the advent of technological progression has led to advanced research in the use of genomic and proteomic expression profiling to simultaneously assess biomarkers of radiation exposure. We describe here the technical advantages of the Luminex(TM) 100 system relative to traditional methods and its potential as a tool to simultaneously profile multiple proteins induced by ionizing radiation. The development of such a bioassay would provide more relevant post-translational dynamics of stress response and will impart important implications in the advancement of space and other radiation contact monitoring. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Center JSC↗
NASA NTRS2004

G2 Chromatid Damage and Repair Kinetics in Normal Human Fibroblast Cells Exposed to Low-or High-LET Radiation

Radiation-induced chromosome damage can be measured in interphase using the Premature Chromosome Condensation (PCC) technique. With the introduction of a new PCC technique using the potent phosphatase inhibitor calyculin-A, chromosomes can be condensed within five minutes, and it is now possible to examine the early damage induced by radiation. Using this method, it has been shown that high-LET radiation induces a higher frequency of chromatid breaks and a much higher frequency of isochromatid breaks than low-LET radiation. The kinetics of chromatid break rejoining consists of two exponential components representing a rapid and a slow time constant, which appears to be similar for low- and high- LET radiations. However, after high-LET radiation exposures, the rejoining process for isochromatid breaks influences the repair kinetics of chromatid-type breaks, and this plays an important role in the assessment of chromatid break rejoining in the G2 phase of the cell cycle.

Kawata, T.↗
NASA NTRS2004

Comparison of Genotoxic Damage in Monolayer Cell Cultures and Three-Dimensional Tissue-Like Cell Assemblies

Assessing the biological risks associated with exposure to the high-energy charged particles encountered in space is essential for the success of long-term space exploration. Although prokaryotic and eukaryotic cell models developed in our laboratory and others have advanced our understanding of many aspects of genotoxicity, in vitro models are needed to assess the risk to humans from space radiation insults. Such models must be representative of the cellular interactions present in tissues and capable of quantifying I genotoxic damage. Toward this overall goal, the objectives of this study were to examine the effect of the localized microenvironment of cells, cultured as either 2-dimensional (2D) monolayers or 3-dimensional (3D) aggregates, on the rate and type of genotoxic damage resulting from exposure to iron charged particles, a significant portion of space radiation. We used rodent transgenic cell lines containing 50-70 copies of a LacI transgene to provide the enhanced sensitivity required to quantify mutational frequency and type in the 1,100-bp LacI target as well as assessment of DNA,damage to the entire 45-kbp construct. Cultured cells were exposed to high-ener~ir on charged particles at Brookhaven National Laboratory s Alternating Gradient Synchrotron facility for a total dose of 0, 0.1, 0.25,0.5, 1.0, or 2.0 Gy and allowed to recover for 0, 1, or 7 days, after which mutational type and frequency were evaluated. The mutational frequency was found to be higher in 3D samples than in 2D samples at all radiation doses. Mutational frequency also was higher at 7 days after irradiation than immediately after exposure. DNA sequencing of the mutant targets revealed that deletional mutations contributed an increasingly high percentage (up to 27%) of all mutations in cells as the dose was increased from 0.5 to 2 Gy. Several mutants also showed large and complex deletions in multiple locations within the Lac1 target. However, no differences in mutational type were found between the 2D and the 3D samples. These 3D tissue-like model systems can reduce the uncertainty involved in extrapolating risk between in vitro cellular and in vivo models.

Behravesh, E.↗
NASA NTRS2002

Karyotypes of Human Lymphocytes Exposed to High-Energy Iron Ions

Chromosomal aberrations were analyzed using multicolor fluorescence in situ hybridization (mFISH) in human peripheral blood lymphocytes after in vitro exposure to gamma rays or accelerated (56)Fe ions (1 GeV/nucleon, 145 keV/microm) at Brookhaven National Laboratory (Upton, NY). Doses of 0.3 and 3 Gy were used for both radiation types. Chromosomes were prematurely condensed by a phosphatase inhibitor (calyculin A) to avoid the population selection bias observed at metaphase as a result of the severe cell cycle delays induced by heavy ions. A total of 1053 karyotypes (G(2) and M phases) were analyzed in irradiated lymphocytes. Results revealed different distribution patterns for chromosomal aberrations after low- and high-LET radiation exposures: Heavy ions induced a much higher fraction of cells with multiple aberrations, while the majority of the aberrant cells induced by low doses of gamma rays contained a single aberration. The high fraction of complex-type exchanges after heavy ions leads to an overestimation of simple-type asymmetrical interchanges (dicentrics) from analysis of Giemsa-stained samples. However, even after a dose of 3 Gy iron ions, about 30% of the cells presented no complex-type exchanges. The involvement of individual chromosomes in exchanges was similar for densely and sparsely ionizing radiation, and no statistically significant evidence of a nonrandom involvement of specific chromosomes was detected.

NASA Center JSC↗
NASA NTRS2002

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Non-NASA Center↗
NASA NTRS2001

Chromosome aberrations in the blood lymphocytes of astronauts after space flight

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.

NASA Center JSC↗
NASA NTRS2001

Probabilities of radiation-induced inter- and intrachromosomal exchanges and their dependence on the DNA content of the chromosome

A biophysical model has been developed that is based on the assumptions that an interphase chromosome occupies a spherical territory and that chromosome exchanges are formed by the misrejoining of two DNA double-strand breaks induced within a defined interaction distance. The model is used to explain the relative frequencies of inter- and intrachromosomal exchanges and the relationship between radiation-induced aberrations in individual chromosomes and the DNA content of the chromosome. Although this simple model predicts a higher ratio of inter- to intrachromosomal exchanges for low-LET radiation than for high-LET radiation, as has been suggested by others, we argue that the comparison of the prediction of the model with experimental results is not straightforward. With the model, we also show that the probability of the formation of interchromosomal exchanges is proportional to the "surface area" of the chromosome domain plus a correction term. The correction term is small if the interaction distance is less than 1 microm for both low- and high-LET radiations.

NASA Center JSC↗
NASA NTRS2001

Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts

We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.

NASA Center JSC↗
NASA NTRS2001

Relationship between radiation-induced aberrations in individual chromosomes and their DNA content: effects of interaction distance

PURPOSE: To study the effect of the interaction distance on the frequency of inter- and intrachromosome exchanges in individual chromosomes with respect to their DNA content. Assumptions: Chromosome exchanges are formed by misrejoining of two DNA double-strand breaks (DSB) induced within an interaction distance, d. It is assumed that chromosomes in G(0)/G(1) phase of the cell cycle occupy a spherical domain in a cell nucleus, with no spatial overlap between individual chromosome domains. RESULTS: Formulae are derived for the probability of formation of inter-, as well as intra-, chromosome exchanges relating to the DNA content of the chromosome for a given interaction distance. For interaction distances <1 microm, the relative frequency of interchromosome exchanges predicted by the present model is similar to that by Cigarran et al. (1998) based on the assumption that the probability of interchromosome exchanges is proportional to the "surface area" of the chromosome territory. The "surface area" assumption is shown to be a limiting case of d-->0 in the present model. The present model also predicts that the probability of intrachromosome exchanges occurring in individual chromosomes is proportional to their DNA content with correction terms. CONCLUSION: When the interaction distance is small, the "surface area" distribution for chromosome participation in interchromosome exchanges has been expected. However, the present model shows that for the interaction distance as large as 1 microm, the predicted probability of interchromosome exchange formation is still close to the surface area distribution. Therefore, this distribution does not necessarily rule out the formation of complex chromosomal aberrations by long-range misrejoining of DSB.

Non-programmatic↗