Biomedical subjects

H Nikjoo

Publications and source records attributed to H Nikjoo.

At least 37 records · Page 2Linked to original sources

PubMed1999

Applications of amorphous track models in radiation biology.

The average or amorphous track model uses the response of a system to gamma-rays and the radial distribution of dose about an ion's path to describe survival and other cellular endpoints from proton, heavy ion, and neutron irradiation. This model has been used for over 30 years to successfully fit many radiobiology data sets. We review several extensions of this approach that address objections to the original model, and consider applications of interest in radiobiology and space radiation risk assessment. In the light of present views of important cellular targets, the role of target size as manifested through the relative contributions from ion-kill (intra-track) and gamma-kill (inter-track) remains a critical question in understanding the success of the amorphous track model. Several variations of the amorphous model are discussed, including ones that consider the radial distribution of event-sizes rather than average electron dose, damage clusters rather than multiple targets, and a role for repair or damage processing.

Animals↗

PubMed1999

A Monte Carlo code for positive ion track simulation.

An ion interaction model has been described for simulating positive ion tracks in a variety of media with the capability of interfacing with several secondary electron transport codes. Data are presented for single-and double-differential cross-sections, binding energies, probability density distribution for delocalisation parameters for conductors and tissue, branching ratios and ionisation efficiencies for water vapour and liquid water.

Computer Simulation↗

PubMed1999

Reduction of the gamma-ray component from 252Cf fission neutron source--optimization for biological irradiations and comparison with MCNP code.

Gamma-rays contribute 33% of the absorbed dose from an unfiltered 252Cf fission neutron source. To reduce this gamma-ray component and to enable radiobiological experiments at as high a dose rate as possible, Monte Carlo calculations for several filter materials (Al, Fe, Pb and concrete) have been made using MCNP neutron and photon transport code version 4a. A lead filter of thickness 4 cm was found to reduce the gamma-ray component to 6.7% of the total dose whilst reducing the neutron dose by only about 10%. Such a filter was installed at the MRC 252Cf neutron irradiation facility and dosimetric measurements were made using a TE-TE chamber and a 7LiF(Mg, Cu, P) TLD. Monte Carlo simulations agree with experimental measurements of neutron and gamma-ray doses within 6%. V79-4 Chinese hamster cells were irradiated with lead-filtered and unfiltered neutrons and also with 60Co gamma-rays at two dose rates. The survival fraction obtained for each radiation was consistent with the reduced gamma-ray dose. The relative biological effectiveness for neutrons alone, corrected for gamma-ray effects, was found to be 9.2 +/- 3.4 from the initial slopes and 3.1 +/- 0.5 at 10% survival, both relative to the acute gamma-rays.

Animals↗

PubMed1999

RBE-LET relationships in mutagenesis by ionizing radiation.

The paper considers the relationship between the quality of radiation and biological lesions produced by ionizing radiation. The paper provides a brief review of the modelling of induction of strand breakage, chromosome aberration, revertant mutation in bacteria and Drosophila melanogaster. Experimental data are presented for the relative biological effectiveness of helium ions and alpha-particles for mutation induction and genome lethality in Escherichia coli. The paper examines the relationship between the mutational events and LET. The RBE-LET values for T4 phage, E. coli WP2 and mwh (multiple wing hair) show dependency on LET while the wi (white-ivory) allele mutants show no dependency.

Animals↗

PubMed1999

Comparison and assessment of electron cross sections for Monte Carlo track structure codes.

The purpose of this study was to make an intercomparison and assessment of cross sections for electrons in water used in electron track structure codes. This study is intended to shed light on the extent to which the differences between the input data and physical and chemical assumptions influence the outcome in biophysical modeling of radiation effects. Ionization cross sections and spectra of secondary electrons were calculated by various theories. The analyses were carried out for water vapor cross sections, as these are more abundant and readily available. All suitable published experimental total ionization cross sections were fitted by an appropriate function and used for generation of electron tracks. Three sets of compiled data were used for comparison of total excitation cross sections and mean excitation energy. The tracks generated by a Monte Carlo track code, using various combinations of cross sections, were compared in terms of radial distributions of interactions and point kernels. The spectrum of secondary electrons emitted by the ionization process was found to be the factor that has the most influence on these quantities. A different set of cross sections for excitation and elastic scattering did not affect the electron track structure as much as did ionization cross sections. It is concluded that all codes, using different cross sections and in different phase, currently used for biophysical modeling exhibit close similarities for energy deposition in larger size targets while appreciable differences are observed in B-DNA-size targets. We recommend fitted functions to all available suitable experimental data for the total ionization and elastic cross sections. We conclude that most codes produce tracks in reasonable agreement with the macroscopic quantities such as total stopping power and total yield of strand breaks. However, we predict differences in frequencies of clustering in tracks from the different models.

DNA Damage↗

PubMed1998

A novel algorithm for tracing the interaction of a track with molecular targets--use of Delaunay triangulation.

This paper describes an efficient method for tracing interactions between a radiation track and molecular targets in a cell or nucleus. The method is efficient because it ensures that a minimal subset of interactions in the track needs to be tested for each score. It is most useful for high-energy particles since the number of interactions and range of the tracks increase with particle energy. In this method, the set of interactions, i.e. the track, is considered as a collection of points in three-dimensional space. This set, together with the eight vertices of a bounding box, is discretised as a collection of tetrahedra, each of which satisfies the Delaunay criterion. Because of the geometric properties of these tetrahedra, only those points which are connected to vertices of tetrahedra through which the target passes need be tested for scoring. An efficient algorithm is used to follow the track through the cell or the nucleus. The main benefit of the method is that it eliminates the need to test those interactions which are geometrically distant from the target. In particular, in cases where there are no interactions in the target, very few interactions need to be checked.

Algorithms↗

PubMed1998

The relative biological effectiveness of accelerated carbon ions with different LET for inducing mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila larvae.

PURPOSE: To evaluate the relative biological effectiveness (RBE) of accelerated carbon ions generated with a synchrotron for inducing mutations as a function of linear energy transfer (LET), using the loss of heterozygosity for wing-hair mutations and the reversion of the mutant white-ivory eye-colour in Drosophila melanogaster. MATERIALS AND METHODS: The measurements were made using a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-colour clones can be detected simultaneously in the same fly. Larvae were irradiated at the age of 72+/-6 h post-oviposition with X-rays or carbon ions with LET values of 13, 60 and 95 keV/microm. RESULTS: The RBE of carbon ions for producing wing-hair mosaic spots increased with increasing LET values. The RBE for the induction of eye-colour mutants did not change with LET. The estimated RBE values were found to be in the range 2 to 6.5 for the wing-hair and nearly unity for the eye-colour mosaic spot mutations. CONCLUSIONS: RBE-LET relationships were obtained for the induction of wing-hair and eye-colour mosaic spots. These relationships suggest that more complex types of DNA damage, such as nonrejoinable strand breaks that increase with LET, may be responsible for inducing the wing-hair mutation, while more simple forms of molecular damage induce reversion in the white-ivory allele.

Animals↗

PubMed1998

Track structure in radiation biology: theory and applications.

PURPOSE: A brief review is presented of the basic concepts in track structure and the relative merit of various theoretical approaches adopted in Monte-Carlo track-structure codes are examined. In the second part of the paper, a formal cluster analysis is introduced to calculate cluster-distance distributions. METHOD: Total experimental ionization cross-sections were least-square fitted and compared with the calculation by various theoretical methods. Monte-Carlo track-structure code Kurbuc was used to examine and compare the spectrum of the secondary electrons generated by using functions given by Born-Bethe, Jain-Khare, Gryzinsky, Kim-Rudd, Mott and Vriens' theories. The cluster analysis in track structure was carried out using the k-means method and Hartigan algorithm. RESULTS: Data are presented on experimental and calculated total ionization cross-sections: inverse mean free path (IMFP) as a function of electron energy used in Monte-Carlo track-structure codes; the spectrum of secondary electrons generated by different functions for 500 eV primary electrons; cluster analysis for 4 MeV and 20 MeV alpha-particles in terms of the frequency of total cluster energy to the root-mean-square (rms) radius of the cluster and differential distance distributions for a pair of clusters; and finally relative frequency distribution for energy deposited in DNA, single-strand break and double-strand breaks for 10MeV/u protons, alpha-particles and carbon ions. CONCLUSIONS: There are a number of Monte-Carlo track-structure codes that have been developed independently and the bench-marking presented in this paper allows a better choice of the theoretical method adopted in a track-structure code to be made. A systematic bench-marking of cross-sections and spectra of the secondary electrons shows differences between the codes at atomic level, but such differences are not significant in biophysical modelling at the macromolecular level. Clustered-damage evaluation shows: that a substantial proportion of dose ( 30%) is deposited by low-energy electrons; the majority of DNA damage lesions are of simple type; the complexity of damage increases with increased LET, while the total yield of strand breaks remains constant; and at high LET values nearly 70% of all double-strand breaks are of complex type.

Alpha Particles↗

PubMed1998

The effects of delta rays on the number of particle-track traversals per cell in laboratory and space exposures.

It is a common practice to estimate the number of particle-track traversals per cell or cell nucleus as the product of the ion's linear energy transfer (LET) and cell area. This practice ignores the effects of track width due to the lateral extension of delta rays. We make estimates of the number of particle-track traversals per cell, which includes the effects of delta rays using radial cutoffs in the ionization density about an ion's track of 1 mGy and 1 cGy. Calculations for laboratory and space radiation exposures are discussed, and show that the LET approximation provides a large underestimate of the actual number of particle-track traversals per cell from high-charge and energy (HZE) ions. In light of the current interest in the mechanisms of radiation action, including signal transduction and cytoplasmic damage, these results should be of interest for radiobiology studies with HZE ions.

Cells↗

PubMed1997

Computational modelling of low-energy electron-induced DNA damage by early physical and chemical events.

Modelling and calculations are presented as a first step towards mechanistic interpretation and prediction of radiation effects based on the spectrum of initial DNA damage produced by low energy electrons (100 eV-4.5 keV) that can be compared with experimental information. Relative yields of single and clustered strand breaks are presented in terms of complexity and source of damage, either by direct energy deposition or by reaction of OH radicals, and dependence on the activation probability of OH radicals and the amount of energy required to give a single strand break (ssb). Data show that the majority of interactions in DNA do not lead to damage in the form of strand breaks and when they do occur, they are most frequently simple ssb. However, for double-strand breaks (dsb), a high proportion (approximately 30%) are of more complex forms, even without considering additional complexity from base damage. The greater contribution is from direct interactions in the DNA but reactions of OH radicals add substantially to this, both in terms of the total number of breaks and in increasing the complexity within a cluster. It has been shown that the lengths of damaged segments of DNA from individual electron tracks tend to be short, indicating that consequent deletion length (simply by loss of a fragment between nearby dsb) would be short, very seldom exceeding a few tens of base pairs.

Computer Simulation↗

PubMed1997

The influence of track structure on the understanding of relative biological effectiveness for induction of chromosomal exchanges in human lymphocytes.

A biophysical model has been applied to describe the production of exchange chromosomal aberrations (dicentrics) in human lymphocytes by radiations of different qualities. The model includes a detailed description of the energy deposition pattern in the form of computer-generated tracks. Energy deposition events are further converted to DNA double-strand breaks (DSBs). Formation of chromosomal exchanges is modeled in competition with repair in a distance-dependent manner with breaks in proximity being most likely to interact. We demonstrate that an assumption of an RBE > 1 for production of DSBs at higher LET leads to a significant increase with LET of both the linear and the quadratic coefficients of the dose response for exchange formation. The latter is not supported experimentally and argues against high RBE values for production of DSBs, at least for those breaks involved in chromosomal exchanges. Assuming that the RBE for production of DSBs is unity, the calculated dose-response curves conformed to experimental data for 60Co gamma rays, 250 kVp X rays and 8.7 MeV protons. The linear coefficient for 23.5 MeV 3He ions is underpredicted. The model predicts that a quadratic term in the dose response for exchange aberrations should be observed at LET values of 20-30 keV/microm. The curvature is not observed experimentally, and the contradiction is discussed.

Alpha Particles↗

PubMed1996

On the mechanism of the formation of chromosomal aberrations by ionising radiation.

The results of applying a biophysical model to describe the production of chromosomal aberrations in human lymphocytes are presented. The model describes energy deposition in cell nuclei, the conversion to DNA double-strand breaks, and the repair and misrepair of those breaks to form aberrations. The repair and misrepair of double-strand breaks are expressed as a competition process based on the concept that the probability of exchange depends upon the spatial separation of the breaks. Results are restricted to photon irradiations. We show that the model leads to the familiar linear-quadratic equation for the dependence of exchange aberration yield on dose. Exchanges between two DNA breaks along the same track determine the linear term, and exchanges between those in different tracks determine the quadratic term. We demonstrate the importance of electron track structure in the prediction of the linear term and show that the low-dose RBE between x- and gamma-rays depends not only on the physical description of the track but also the biological repair function. For intratrack exchanges, we show that the double-strand breaks are very close, on average about 30 nm apart. For intertrack exchanges, the mean separation of breaks is calculated to be about 2 mu m. There is a clear separation of the two modes of action. In addition, the increased effectiveness of the track ends of electrons is shown.

Cell Nucleus↗

PubMed1996

Energy spectra of secondary electrons in water vapour.

The purpose of this work is to present a method for the calculation of secondary electron spectra generated by photons in water vapour in the energy region from 10 eV to 10 MeV. The cross sections below and above 1 keV have been treated separately. Examples are given for secondary electron spectra for low-energy photons, < 100 eV, in which all electrons are photoelectrons, and at higher energy regions, such as for 60Co photons. The spectrum of the first generation of secondary electrons, produced by 60Co photons, which are mainly due to incoherent scattering, was fitted with a set of polynomial functions which can be used as input for electron radiation action calculations.

Electrons↗

PubMed1996

Modelling of Auger-induced DNA damage by incorporated 125I.

We have analyzed a newly available high resolution and precision repeat of the original Martin and Haseltine experiment which includes the influence of DMSO on the results. The new model includes the production and diffusion of radical species and .OH radical attack on DNA as well as the direct hits. Calculations of single-strand breaks use individual Auger electron along with the tracks of electrons and radical species superimposed on an atomistic model of B-DNA. Comparison of the preliminary calculations with the experiment supports the earlier choice of data for the amount of energy required to produce a single-strand break, i.e. 17.5 eV. In a separate simulation we found that an average of less than two ionizations inducing a single-strand break gave the best fit to experimental data. Direct hits were found to be predominantly occurring at short range while the damage by .OH radicals was mainly of the long-range type.

DNA, Single-Stranded↗

PubMed1995

A knowledge-based model of DNA hydration.

The aqueous hydration of DNA is an important aspect of its structure, which is of direct relevance to mechanisms of radiation damage. We have made a quantitative analysis of solvent interactions within hydrogen bonding distance of polar atoms of oligonucleotides using 12 B-DNA oligonucleotide crystal structures. The distribution of water molecules around the four bases, the sugar residues and the phosphate groups were generated and analysed both qualitatively and quantitatively. These data have then been used in a knowledge-based method to generate the likely hydration sites around a canonical B-DNA conformation in order to generate models of use in track studies of radiation damage.

Base Sequence↗

PubMed1994

Comparison of various Monte Carlo track structure codes for energetic electrons in gaseous and liquid water.

Cross section for kurbuc, a Monte Carlo track structure code simulating histories of electrons, interaction by interaction, in the energy range of 10 eV to 10 MeV, have been presented. Comparisons have been made for four independent Monte Carlo track structure codes for energetic electrons in gaseous and liquid water. The comparisons have been made in terms of point kernels for interactions and energy absorbed, and frequencies of energy depositions in cylindrical volumes of sizes similar to biological macromolecules. Comparisons have been made for 100 eV, 300 eV, 500 eV, 1 keV, 10 keV and 100 keV monoenergetic electrons. The four electron codes used in this study are moca8b and kurbuc for water vapour and orec and cpa100 for liquid water. A summary of cross sections, used in each code has been presented. The comparisons show similarities and differences in clustering properties of the four codes.

Chromatin↗

PubMed1994

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

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

Aluminum↗

PubMed1994

Modelling of radiation-induced DNA damage: the early physical and chemical event.

A Monte Carlo track structure calculation of single- and double-strand breaks induced by direct energy deposition in DNA and by interacting diffusible .OH radicals with DNA has been made for low energy electrons. The .OH radicals generated within 4 nm of linear segments of DNA were diffused in order to mimic the mean diffusion distance in the cellular environment. The reactions of the radical species .OH, .H and e-aq were included in this study. The calculated values for the yield of single- and double-strand breaks have been compared with experimentally determined values from the literature. The calculations indicate, too, that the majority of dsb have additional associated damage, constituting clustered lesions of varying complexity.

DNA↗