Engineering topics

Cucinotta, F. A.

Publications and source records attributed to Cucinotta, F. A..

At least 19 records

NASA NTRS2013

Estimation of the Dose and Dose Rate Effectiveness Factor

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Chappell, L.↗

NASA NTRS2012

The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

George, K.↗

NASA NTRS2011

Calculation of Dose Deposition in 3D Voxels by Heavy Ions and Simulation of gamma-H2AX Experiments

The biological response to high-LET radiation is different from low-LET radiation due to several factors, notably difference in energy deposition and formation of radiolytic species. Of particular importance in radiobiology is the formation of double-strand breaks (DSB), which can be detected by -H2AX foci experiments. These experiments has revealed important differences in the spatial distribution of DSB induced by low- and high-LET radiations [1,2]. To simulate -H2AX experiments, models based on amorphous track with radial dose are often combined with random walk chromosome models [3,4]. In this work, a new approach using the Monte-Carlo track structure code RITRACKS [5] and chromosome models have been used to simulate DSB formation. At first, RITRACKS have been used to simulate the irradiation of a cubic volume of 5 m by 1) 450 1H+ ions of 300 MeV (LET 0.3 keV/ m) and 2) by 1 56Fe26+ ion of 1 GeV/amu (LET 150 keV/ m). All energy deposition events are recorded to calculate dose in voxels of 20 m. The dose voxels are distributed randomly and scattered uniformly within the volume irradiated by low-LET radiation. Many differences are found in the spatial distribution of dose voxels for the 56Fe26+ ion. The track structure can be distinguished, and voxels with very high dose are found in the region corresponding to the track "core". These high-dose voxels are not found in the low-LET irradiation simulation and indicate clustered energy deposition, which may be responsible for complex DSB. In the second step, assuming that DSB will be found only in voxels where energy is deposited by the radiation, the intersection points between voxels with dose > 0 and simulated chromosomes were obtained. The spatial distribution of the intersection points is similar to -H2AX foci experiments. These preliminary results suggest that combining stochastic track structure and chromosome models could be a good approach to understand radiation-induced DSB and chromosome aberrations.

Plante, I.↗

NASA NTRS2011

The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, Ti-48-ions with energies ranging from 240 to 1000 MeV/u, or to Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Si beams in this study ranged from 48 to 158 keV/ m, the LET of the Ti ions ranged from 107 to 240 keV/micron, and the LET of the Fe-ions ranged from 145 to 440 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to gamma-rays. The estimates of RBEmax values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, 21.4+/-1.7 to 28.3+/-2.4 for Ti ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBEmax value for Fe ions was obtained with the 600 MeV/u beam, the highest RBEmax value for Ti ions was obtained 1000 MeV/u beam, and the highest RBEmax value for Si ions was obtained with the 170 MeV/u beam. For Si and Fe ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreasing with further increase in LET. Additional studies for low doses Si-28-ions down to 0.02 Gy will be discussed.

Hada, M.↗

NASA NTRS2011

Cancer Risk Estimates from Space Flight Estimated Using Yields of Chromosome Damage in Astronaut's Blood Lymphocytes

To date, cytogenetic damage has been assessed in blood lymphocytes from more than 30 astronauts before and after they participated in long-duration space missions of three months or more on board the International Space Station. Chromosome damage was assessed using fluorescence in situ hybridization whole chromosome analysis techniques. For all individuals, the frequency of chromosome damage measured within a month of return from space was higher than their preflight yield, and biodosimetry estimates were within the range expected from physical dosimetry. Follow up analyses have been performed on most of the astronauts at intervals ranging from around 6 months to many years after flight, and the cytogenetic effects of repeat long-duration missions have so far been assessed in four individuals. Chromosomal aberrations in peripheral blood lymphocytes have been validated as biomarkers of cancer risk and cytogenetic damage can therefore be used to characterize excess health risk incurred by individual crewmembers after their respective missions. Traditional risk assessment models are based on epidemiological data obtained on Earth in cohorts exposed predominantly to acute doses of gamma-rays, and the extrapolation to the space environment is highly problematic, involving very large uncertainties. Cytogenetic damage could play a key role in reducing uncertainty in risk estimation because it is incurred directly in the space environment, using specimens from the astronauts themselves. Relative cancer risks were estimated from the biodosimetry data using the quantitative approach derived from the European Study Group on Cytogenetic Biomarkers and Health database. Astronauts were categorized into low, medium, or high tertiles according to their yield of chromosome damage. Age adjusted tertile rankings were used to estimate cancer risk and results were compared with values obtained using traditional modeling approaches. Individual tertile rankings increased after space flight and analysis of follow up samples indicated that the tertile rankings remained in the high category for more than 50% of the individuals assessed so far. Crewmembers that shift and remain in the high category are projected to have increased life-time cancer risk.

George, Kerry A.↗

NASA NTRS2011

Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would otherwise die or be rendered reproductively inactive in 2-D culture.

Patel, Z. S.↗

NASA NTRS2011

Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

Ponomarev, A. L.↗

NASA NTRS2011

The Distribution of Chromosomal Aberrations in Human Cells Predicted by a Generalized Time-Dependent Model of Radiation-Induced Formation of Aberrations

New experimental data show how chromosomal aberrations for low- and high-LET radiation are dependent on DSB repair deficiencies in wild-type, AT and NBS cells. We simulated the development of chromosomal aberrations in these cells lines in a stochastic track-structure-dependent model, in which different cells have different kinetics of DSB repair. We updated a previously formulated model of chromosomal aberrations, which was based on a stochastic Monte Carlo approach, to consider the time-dependence of DSB rejoining. The previous version of the model had an assumption that all DSBs would rejoin, and therefore we called it a time-independent model. The chromosomal-aberrations model takes into account the DNA and track structure for low- and high-LET radiations, and provides an explanation and prediction of the statistics of rare and more complex aberrations. We compared the program-simulated kinetics of DSB rejoining to the experimentally-derived bimodal exponential curves of the DSB kinetics. We scored the formation of translocations, dicentrics, acentric and centric rings, deletions, and inversions. The fraction of DSBs participating in aberrations was studied in relation to the rejoining time. Comparisons of simulated dose dependence for simple aberrations to the experimental dose-dependence for HF19, AT and NBS cells will be made.

Ponomarev, Artem L.↗

NASA NTRS2011

Non-Target Effect for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Doses of High LET Radiation

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (.01 - 0.2 Gy) of 170 MeV/u Si-28-ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The curves for doses above 0.1 Gy were more than one ion traverses a cell showed linear dose responses. However, for doses less than 0.1 Gy, Si-28-ions showed no dose response, suggesting a non-targeted effect when less than one ion traversal occurs. Additional findings for Fe-56 will be discussed.

Hada, Megumi↗

NASA NTRS2011

Modularized TGFbeta-Smad Signaling Pathway

The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

Li, Yongfeng↗

NASA NTRS2011

The Biological Effectiveness of Four Energies of Neon Ions for the Induction of Chromosome Damage in Human Lymphocytes

Chromosomal aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to neon ions at energies of 64, 89, 142, or 267. The corresponding LET values for these energies of neon ranged from 38-103 keV/micrometers and doses delivered were in the 10 to 80 cGy range. Chromosome exchanges were assessed in metaphase and G2 phase cells at first division after exposure using fluorescence in situ hybridization (FISH) with whole chromosome probes and dose response curves were generated for different types of chromosomal exchanges. The yields of total chromosome exchanges were similar for the 64, 89, and 142 MeV exposures, whereas the 267 MeV/u neon with LET of 38 keV/micrometers produced about half as many exchanges per unit dose. The induction of complex type chromosome exchanges (exchanges involving three or more breaks and two or more chromosomes) showed a clear LET dependence for all energies. The ratio of simple to complex type exchanges increased with LET from 18 to 51%. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The RBE(sub max) values for total chromosome exchanges for the 64 MeV/u was around 30.

George, Kerry↗

NASA NTRS2011

Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

George, K.↗

NASA NTRS2011

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

Hada, M.↗

NASA NTRS2010

The Biological Effectiveness of Silicon Ions is Significantly Higher than Iron Ions for the Induction of Chromosome Damage in Human Lymphocytes

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, or Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Fe beams in this study ranged from 145 to 440 keV/micron and the LET Si ions ranged from 48 to 158 keV/micron. Doses delivered were in the 10 to 200 cGy range. Dose response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The estimates of RBE(sub max) values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBE(sub max) value for Fe ions was obtained with the 600 Mev/u beam and 170 MeV/u beam produced the highest RBE(sub max) value for Si ions. For both ions the RBE(sub max) values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreased with further increase in LET.

George, Kerry↗

NASA NTRS2010

Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts: Persistence of Damage After Flight and the Effects of Repeat Long Duration Missions

Cytogenetic damage was assessed in blood lymphocytes from astronauts before and after they participated in long-duration space missions of three months or more. The frequency of chromosome damage was measured by fluorescence in situ hybridization (FISH) chromosome painting before flight and at various intervals from a few days to many months after return from the mission. For all individuals, the frequency of chromosome exchanges measured within a month of return from space was higher than their prefight yield. However, some individuals showed a temporal decline in chromosome damage with time after flight. Statistical analysis using combined data for all astronauts indicated a significant overall decreasing trend in total chromosome exchanges with time after flight, although this trend was not seen for all astronauts and the yield of chromosome damage in some individuals actually increased with time after flight. The decreasing trend in total exchanges was slightly more significant when statistical analysis was restricted to data collected more than 220 days after return from flight. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from three crewmembers who has participated in two separate long-duration space missions provide limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

George, Kerry↗

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.↗

NASA NTRS2010

Cytogenetic Biodosimetry Using the Blood Lymphocytes of Astronauts

Cytogenetic analysis of blood lymphocytes remains the most sensitive and reliable method available for in vivo assessment of the biological effects of exposure to radiation and provides the most informative measurement of radiation induced health risks. To date chromosome damage has been assessed in lymphocytes from more than 30 astronauts before and after they participated in long-duration space missions of three months or more on board the International Space Station. For all individuals, the frequency of chromosome damage measured within a month of return from space was higher than their prefight yield and biodosimetry estimates lie within the range expected from physical dosimetry. Biodosimetry data provides a direct measurement of space radiation damage, which takes into account individual radiosensitivity in the presence of confounding factors such as microgravity and other stress conditions. In contrast to physical measurements, which are external to body and require multiple devices to detect all radiation types all of which have poor sensitivity to neutrons, biodosimetry is internal and includes the effects of shielding provided by the body itself plus chromosome damage shows excellent sensitivity to protons, heavy ions, and neutrons. In addition, chromosome damage is reflective of cancer risk and biodosimetry values can therefore be used to validate and develop risk assessment models that can be used to characterize excess health risk incurred by crewmembers. A review of astronaut biodosimetry data will be presented along with recent findings on the persistence of space radiation induced chromosome damage and the cytogenetic effects of repeat long duration missions

George, Kerry↗

NASA NTRS2010

The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to 28Si- ions with energies ranging from 90 to 600 MeV/u, or to 56Fe-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Fe beams in this study ranged from 145 to 440 keV/micron and the LET of the Si ions ranged from 48 to 158 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to -rays. The estimates of RBE(sub max) values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBE(sub max) value for Fe ions was obtained with the 600-Mev/u beam, and the highest RBE(sub max) value for Si ions was obtained with the 170 MeV/u beam. For both ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/ m for Si, and decreasing with further increase in LET. Additional studies for low doses 28Si-ions down to 0.02 Gy will be discussed.

Hada, M.↗