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Biomedical subjects

E Pomplun

Publications and source records attributed to E Pomplun.

13 recordsLinked to original sources
PubMed2002

Computer simulation of 57Fe bleomycin auger effects in DNA.

The antibiotic bleomycin binds to the DNA and induces double strand breaks (DSBs). To increase the cleavages. 57Fe is used to form a complex suitable for Mössbauer effect. The de-excitation of the resonant excited 57Fe nucleus releases Auger electrons and X rays. The goal of this work is to evaluate the increase in yield of DSBs due to the 57Fe, using Monte Carlo simulation methods. Particles spectra and the yields of single strand breaks (SSBs) and DSBs were calculated by considering direct events on DNA and reaction of all radical species generated in the radiolysis of its environment. The Auger spectrum shows a large number of electrons with energies below 100 eV, mainly responsible for direct damage, while another group around 600-700 eV is responsible for indirect damage effects. Bleomycin receives about one fourth of the energy deposited in DNA and an average of 0.65 DSB per de-excitation is observed.

Antibiotics, Antineoplastic↗
PubMed2002

Ratio of complex double strand break damage induced by 125IUdR and 123IUdR correlates with experimental in vitro cell killing effectiveness.

The overall cellular damage induced by ionising radiation is determined by the number and spatial distribution of initial ionisations and excitations within the critical volume. This paper focuses on the physical and chemical phase of the radiation action chain following the decay of DNA-bound 123I and 125I. Monte Carlo simulations of these nuclides' decay provide electron emission spectra which are used as input data for track structure calculations. In combination with DNA models, these calculations allow the specific radiation source to be characterised in terms of DNA strand break patterns. The distribution of these patterns indicates that 125I produces much more severe breaks than 123I. The ratio of complex DSBs induced by both iodine isotopes correlates with the differences in cell killing effectiveness reported from in vitro survival experiments.

Animals↗
PubMed2001

Track structures and dose distributions from decays of (131)I and (125)I in and around water spheres simulating micrometastases of differentiated thyroid cancer.

The disintegration of the radionuclides (131)I and (125)I and the subsequent charged-particle tracks left behind in water (as a model substance for a biological cell) are simulated by the Monte Carlo track structure simulation code PARTRAC, using new inelastic electron scattering cross sections for condensed water. Every photon and electron emitted was followed in detail, event by event, down to 10 eV. From the spatial information on the track structures, absorbed dose distributions per (131)I and (125)I decay were calculated in and around water spheres simulating micrometastases as well as in the tissue surrounding such metastases. These radionuclides were assumed to be distributed uniformly inside spheres of different diameters (0.01, 0.03, 0.1, 0.3, 1.0 and 3.0 mm). The respective electron degradation spectra, the nearest-neighbor distance distributions between inelastic events, and the distance distributions for all activations for both iodine radionuclides were calculated. The absorbed fractions of the initial electron energies, absorbed doses and energy depositions, and single-event distributions, F(1)(epsilon), inside the six water spheres described above and in the surrounding tissue were also calculated. The absorbed doses per decay inside the six water spheres, i.e., the calculated S values (listed from 0.01 to 3.0 mm), were 6.8 x 10(-4), 7.2 x 10(-5), 5.5 x 10(-6), 4.9 x 10(-7), 3.1 x 10(-8) and 1.8 x 10(-9) Gy Bq(-1) s(-1) for (131)I, and 3.4 x 10(-3), 1.7 x 10(-4), 5.1 x 10(-6), 2.0 x 10(-7), 5.6 x 10(-9) and 2.2 x 10(-10) Gy Bq(-1) s(-1) for (125)I. It is concluded that, in the treatment of thyroid cancer, the geometrical track structure properties of (125)I might be superior to those of (131)I in micrometastases with diameters less than 0.1 mm; however, in this medical context, many other factors also have to be considered.

Humans↗
PubMed2000

Auger electron spectra--the basic data for understanding the Auger effect.

Understanding the strong radiotoxicity of DNA-incorporated Auger electron-emitting nuclides requires a detailed knowledge of the nuclide's emission spectrum. A Monte Carlo computer code was previously developed to simulate Auger cascades and to provide electron spectra of 125I. To utilize experimental data for a direct validation of these simulations, the code has been adapted for cascades in xenon, which is adjacent to iodine in the table of elements. Only minor modifications of the code were necessary to obtain a very good agreement with the experimental findings. The role of shake-off electrons and the need for energy considerations during the cascades could be demonstrated. A previously published electron spectrum of 125I was recalculated and detailed results are presented here. Furthermore, to consider implications from a molecular binding of the Auger emitter, for the first time semi-empirical quantum mechanical calculations for an iodine-labelled thymine molecule were performed showing that even in the condensed phase a Coulomb explosion cannot be excluded a priori.

DNA Damage↗
PubMed1996

Modelling of initial events and chemical behaviour of species induced in DNA units by Auger electrons from 125I, 123I and carbon.

Auger electron spectra for 123I and 125I generated by Monte Carlo calculation and Auger electrons emitted from carbon after photoelectric effect on its K-shell as well as two DNA models (linear plasmid and nucleosome model) based on x-ray diffraction experiments have been used to simulate the behaviour of all species and radicals created during the physical and the chemical phase of the Auger's transport. By introducing appropriate assumptions for the induction of strand breaks the number of these breaks can also be determined and correlated to experimentally found numbers of lethal events. Efficiency differences between the iodine nuclides themselves and in comparison with the rather monoenergetic Auger electrons from carbon are shown with regard to the direct and indirect effects on the two DNA models. The characteristic products in the physical, chemical and biochemical phase are compared with corresponding results from the literature for low-LET radiation.

Carbon↗
PubMed1994

A nucleosome model for the simulation of DNA strand break experiments.

Using a set of Monte Carlo simulation models, track structures of 125I Auger electrons generated in liquid water are superimposed on a nucleosome DNA model able to precisely localize energy deposition events on sub-molecular units of the DNA strands. After scoring direct hits taking place during the physical phase (at about 10(-15) s) the radiation chemistry of the whole system is simulated between 10(-12) and 10(-8) s, taking into account all reactions between water radio-chemical species, radicals, sub-molecular units of DNA (Ribose, Adenine, Thymine, Guanine, and Cytosine), and scavengers like Tris or Formate ions. The model's possibility to distinguish between direct and indirect hits has been utilized to introduce different assumptions for strand break induction by both hit modes. The number of SSB and DSB as well as their local distribution will be given and compared with experimental and theoretical results from the literature.

Computer Simulation↗
PubMed1994

Low-energy electrons inside active DNA models: a tool to elucidate the radiation action mechanisms.

To postulate radiation action mechanisms and to test them by Monte Carlo simulation, a complex computer model was developed consisting of major components for the generation of a radiation spectrum, biomolecular structures, and electron track structures in liquid water. As the radiation source 125I is employed here; it is an excellent test radiation due to its exactly localized position in the DNA molecule and high biological toxicity as a consequence of the emission of short-ranging Auger electrons. A linear DNA plasmid model (Pomplun 1991) which can actively respond to radical attack (Terrissol and Pomplun 1994) has been modified into a nucleosome model representing the double-helix of DNA with 146 basepairs and more than 9000 atoms surrounding the histones. The introduction of this new target structure allows a more realistic simulation of cellular conditions. Using the model's decay accumulation aspect, the situation of many break and survival experiments can be approximated and the influence of several cellular parameters tested. As a first step, a correlation between the size of energy depositions and strand-break patterns was sought.

DNA↗
PubMed1991

A new DNA target model for track structure calculations and its first application to I-125 Auger electrons.

A DNA target model has been developed, based on the geometrical co-ordinates of individual atoms. This model is used to analyse DNA damage produced by Auger electron tracks from the decay of 125I. The high resolution of this target model enables the distinction between direct and indirect electron hits, i.e. hits inside the atomic volumes of the DNA molecule and those hitting the water molecules assumed in the space between the atomic volumes. Three types of calculations have been performed: (1) the evaluation of the energy deposition in the surroundings of the decaying 125I nuclide demonstrating different fractions of direct to indirect hits at different parts of the DNA molecule (phosphate/sugar strand or bases), (2) a detailed energy deposition pattern in the radiolabelled base, indicating that this most burdened molecule is not necessarily destroyed by direct hits, and (3) a calculation of single- and double- strand breaks by using different threshold values for effective direct and indirect hits, resulting in a good correlation with experimental data on strand break efficiency.

DNA↗
PubMed1987

Auger-electron cascades, charge potential and microdosimetry of iodine-125.

This paper is a contribution to the microdosimetry of I-125. It shows microdosimetric spectra of individual and average disintegrations of I-125 for various target sizes and gives evidence for the relative contributions of energy-deposition events of low and high LET. It further presents information on the relative efficiencies of Auger-electrons and multiple charges in terms of local energy deposition, e.g. to model targets of DNA, and discusses their radiobiological implications, e.g. the microdosimetric understanding of the different efficiencies of specific and random incorporations of I-125. When I-125 is specifically incorporated into DNA, most of the energy deposition events are very large, e.g. above 40 keV/micron for a simulated target volume of 20 nm diameter, regardless of the number and energy of Auger electrons emitted. Therefore it is not necessary, for the discussion of the radiobiological implications, to distinguish between different classes of disintegrations. For unspecific, homogeneous incorporation of I-125 somewhere into tissue, about 20% of the dose to critical targets of 25 nm diameter is made up by disintegrations that happen to occur within these targets. When assuming that other critical targets and target structures can be neglected, this part of the dose will be equally effective as in the case of specific incorporation of I-125 into such target models. In addition, there are the normal, low-LET radiation effects from the other, 80% large fraction of the dose. With this information, for the biological systems and end points for which a short section of the elemental chromatine fiber can be taken as the relevant critical target, it is shown that the expected D37 value for homogeneous unspecific incorporation of I-125 can be estimated when the D37 for specific incorporation in DNA is known. For an example calculation, the estimated D37-value for nonspecific, homogeneous incorporation of I-125 would be about half as effective as specifically incorporated I-125. Thus, the microdosimetric data of the present work show that a high efficiency of homogeneous incorporation of I-125 into the cell nucleus is not necessarily in contradiction with the idea of I-125 disintegrations inside the DNA being the main cause of radiation action.

DNA↗
PubMed1987

A microdosimetric interpretation of the radiobiological effectiveness of 125I and the problem of quality factor.

When considering the microdosimetric energy deposition in small biological targets the Auger electron emitter 125I behaves like a high-LET radiation. For a specific incorporation in sensitive biological volumes of 20 nm in diameter a mean lineal energy of gamma F approximately equal to 270 keV micron-1 has been evaluated. Experimental data on transformation, mutation and chromosome aberration from DNA-bound 125I are interpreted to yield RBE-values, relative to 200 kV X rays, of 32 to 38 (transformations), 1 to 16 (mutations) and 6 to 77 (chromosome aberrations). Thus the RBE for transformation and chromosome aberration tends to be larger than the ICRP recommended high-LET quality factor (Q = 20). The implications of these results for the function Q(L) applied in radiation protection will be discussed.

Animals↗
PubMed1987

A Monte Carlo simulation of Auger cascades.

The energy imparted to biological tissue after the decay of incorporated Auger emitters stems from two sources: (a) energy deposition by the Auger and Coster-Kronig electrons and (b) the charge potential which remains on the multiple ionized atom after the end of the cascade. For the numerical assessment of both the kinetic energy of the released electrons and the charge potential, a new and--for purposes of microdosimetry--precise method is presented. Based on relativistic Dirac-Fock calculations and a rigorous bookkeeping, this method provides a perfect energy balance of the considered atomic system when applied to Monte Carlo simulations of Auger cascades. By comparing the results for charge distribution for krypton and iodine with experimental data and the electron spectrum of 125I with theoretical data, it can be shown that the approach followed in this work is reasonable and appropriate for the determination of the energy deposited by incorporated Auger emitters in small volumes of condensed matter. The total energy deposited by 125I in a volume of 20-nm diameter is 2.03 keV which is made up by multiple ionization (1.07 keV) and energy deposition by the emitted Auger electrons (0.96 keV).

Chemical Phenomena↗
PubMed1987

Some consequences of the Auger effect: fluorescence yield, charge potential, and energy imparted.

The potential energy produced by the Auger cascade due to the charging of atoms is evaluated and incorporated into conventional treatment of energy deposition. A straightforward method for calculating this energy is presented. For the photoelectric interaction the potential energy is shown to be at least as important as L-shell fluorescence in calculating the electron kerma. For radioactive decay by electron capture or internal conversion, it is shown that, for small (less than 100 nm) targets containing the decay, the atomic charging can be the dominant contribution to the total energy deposited in the target.

Bromine↗