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Herwig G Paretzke

Publications and source records attributed to Herwig G Paretzke.

12 recordsLinked to original sources

Simulation of light ion induced DNA damage patterns.

The biophysical simulation code PARTRAC was extended by a module to handle ions heavier than alpha particles. Cross sections for ion-electron interactions were taken from He(++) ions of the same velocity and scaled by Z(eff(2))/4. Calculated linear energy transfer values, radial dose distributions and secondary electron spectra were found in agreement with experimental results. DNA damage due to irradiation of human fibroblast cells by several light ions from H to S was calculated for various energies complemented by 220 kV(p) X rays as reference radiation. With increasing linear energy transfer, the calculated total yield of double-strand breaks per dose showed saturation behaviour at about twice the value for reference radiation. When data analysis methods for experimental double-strand break yield determination were applied to the simulated DNA damage patterns, the two data sets were found in accord. The calculated patterns of DNA damage clusters were analysed on local and regional scale finding regional clusters in closer correlation to experimental cell inactivation data.

Chromatin↗

Biokinetic modeling of uranium in man after injection and ingestion.

Uranium is a naturally occurring primordial radioactive element. Small amounts found in air, water, and food are regularly consumed and inhaled by humans. Even the military, medical, and industrial use of depleted uranium can affect humans. There is an appreciable retention of incorporated uranium in skeleton, kidneys, and liver, and a review of respective effective dose coefficients has been given by the International Commission on Radiological Protection (ICRP) in its "Publication 69"; however, data regarding retention in organs or tissues and rates of urinary and fecal excretion for different age groups are incomplete. Therefore, the present study provides retention data that have been calculated for uranium in all compartments and for urinary and fecal excretion, following acute and chronic injection and ingestion for six age groups. The calculations are based on the current ICRP biokinetic model for uranium, and the data can be plotted by using any mathematical software to obtain the retention data at any time after incorporation or to calculate the internal average organ dose induced by uranium provided that specific absorbed fractions are available. The dynamic relationship of the retention in plasma and blood after intravenously and orally administered uranium can easily be derived from the database for injection and ingestion. The calculated contents of uranium in organs or tissues (using the uranium concentration in foodstuffs published by UNSCEAR for Europeans) are compared with autopsy data available in the literature. According to this model, the whole body of a 75-year-old man contains 7 microg uranium, of which 76% is in the skeleton, 1% in the kidneys, and 2.1% in the liver.

Adolescent↗

Caesium-affected gene expression in Arabidopsis thaliana.

* Excessive caesium can be toxic to plants. Here we investigated Cs uptake and caesium-induced gene expression in Arabidopsis thaliana. * Accumulation was measured in plants grown for 5 wk on agar supplemented with nontoxic and up to toxic levels of Cs. Caesium-induced gene expression was studied by suppression-subtractive hybridization (SSH) and RT-PCR. * Caesium accumulated in leaf rosettes dependent upon the external concentration in the growth media, whereas the potassium concentration decreased in rosettes. At a concentration of 850 microM, Cs plants showed reduced development, and withered with an increase in concentration to 1 mM Cs. SSH resulted in the isolation of 73 clones that were differentially expressed at a Cs concentration of 150 microM. Most of the genes identified belong to groups of genes encoding proteins in stress defence, detoxification, transport, homeostasis and general metabolism, and proteins controlling transcription and translation. * The present study identified a number of marker genes for Cs in Arabidopsis grown under nontoxic Cs concentrations, indicating that Cs acts as an abiotic stress factor.

Arabidopsis↗

Low-level radiocaesium exposure alters gene expression in roots of Arabidopsis.

Radiocaesium is one of the main anthropogenic sources of internal and external exposure to beta- and gamma-radiation (e.g. from global fallout of atmospheric atomic bomb testing and from the Chernobyl reactor accident). Here we investigated gene expression by suppression subtractive hybridization (SSH) and reverse transcription-polymerase chain reaction (RT-PCR) in Arabidopsis thaliana, which was induced by the root uptake of 134Cs. SSH analysis resulted in the isolation of 46 clones that were differentially expressed at 30 Bq cm(-3) 134Cs. Most of the expressed sequence tags identified belonged to genes encoding proteins that were involved in cell growth, cell division and the development of plants, and in proteins controlling translation, general metabolism and stress defence, including a DNA excision repair protein. The accumulation of caesium in plant material was measured in plants grown for 5 wk on agar contaminated by up to 60 Bq cm(-3) 134Cs. 134Cs was found to accumulate, in particular, in leaf rosettes and was dependent on the activity concentration in the growth media. The data indicate that low-level ionizing radiation influences important cellular responses, resulting in a changed gene-expression profile.

Arabidopsis↗

The role of atomic inner shell relaxations for photon-induced DNA damage.

The influence of relaxations of atoms making up the DNA and atoms attached to it on radiation-induced cellular DNA damage by photons was studied by very detailed Monte Carlo track structure calculations, as an unusually high importance of inner shell ionizations for biological action was suspected from reports in the literature. For our calculations cross sections for photons and electrons for inner shell orbitals were newly derived and integrated into the biophysical track structure simulation programme PARTRAC. Both the local energy deposition in a small sphere around the interacting relaxed atom, and the number of relaxations per Gy and Gbp were calculated for several target geometries and many monoenergetic photon irradiations. Elements with the highest order number yielded the largest local energy deposition after interaction. The atomic relaxation after ionization of the L1 shell was found to be more biologically efficient than that of the K shell for high Z atoms. Generally, the number of inner shell relaxations produced by photon irradiation was small in comparison to the total number of double strand breaks generated by such radiation. Furthermore, the energy dependence of the total number of photon-induced and electron-induced relaxations at the DNA atoms does not agree with observed RBE values for different biological endpoints. This suggests that the influence of inner shell relaxations of DNA atoms on radiation-induced DNA damage is in general rather small.

Animals↗

Simulation of (125)I decay in a synthetic oligodeoxynucleotide with normal and distorted geometry and the role of radiation and non-radiation actions.

Within the track structure code PARTRAC, DNA strand break induction by direct and indirect radiation action was calculated for the E. coli catabolite gene activator protein (CAP) DNA complex with (125)I located at the position of the H(5) atom of the cytosine near the center. The shape of the resulting DNA fragment size distributions was found to be in reasonable agreement with corresponding experimental results. However, the calculated yield was considerably lower than the measured one. To study possible reasons for this, recently published experimental data on DNA strand breaks in a 41-mer synthetic oligodeoxynucleotide (oligoDNA) with incorporated (125)I were analyzed aiming at an evaluation of the non-radiation-related component due to the neutralization of the initially highly charged (125m)Te daughter ion. This was done by assuming that the differences between simulated radiation-induced distribution and the measured total fragment size distributions were due to the neutralization process. The neutralization effect defined in this way was found to dominate the strand breakage frequency within a range of 5-7 base pairs around the (125)I decay site on both strands. After implementing this neutralization effect derived from the oligoDNA analysis into the PARTRAC simulation for the CAP-DNA complex, the agreement of the calculated DNA fragment distributions with the corresponding experimental data was considerably improved. The results indicate that DNA conformation may be explored by incorporation of (125)I into the DNA, measurement of fragment size distributions, and comparison with simulation calculation for various hypothetical DNA models.

Computer Simulation↗

Role of DNA organisation and environmental scavenging capacity in the evolution of radiobiological damage: models and simulations.

BACKGROUND AND PURPOSE: Theoretical models and Monte Carlo simulations were developed, aimed to investigate the role played by the organisation of interphase DNA and the environmental scavenging capacity conditions in the induction of radiobiological damage. METHODS: The induction of single- and double-strand breaks by gamma rays impinging on different DNA structures (e.g. linear DNA, SV40 minichromosome and cellular DNA) was simulated as a function of the environment scavenging capacity. Furthermore, yields of chromosome aberrations (CA) induced by gamma rays and light ions were simulated with a purposely developed MC code that explicitly takes into account the DNA higher-order organisation as chromosome territories. RESULTS AND CONCLUSIONS: Simulations performed with the PARTRAC code allowed quantification of the dependence of dsb and ssb both on the target structure, and on the scavenging capacity. The results relative to CA showed the importance of DNA damage complexity (nanometre scale) and interphase chromosome domains (micrometre scale) in the process of aberration formation. Very good agreement was found between the model predictions on ssb, dsb and CA and available experimental data.

Animals↗

Simulation of DNA damage after proton irradiation.

The biophysical radiation track simulation model PARTRAC was improved by implementing new interaction cross sections for protons in water. Computer-simulated tracks of energy deposition events from protons and their secondary electrons were superimposed on a higher-order DNA target model describing the spatial coordinates of the whole genome inside a human cell. Induction of DNA double-strand breaks was simulated for proton irradiation with LET values between 1.6 and 70 keV/microm and various reference radiation qualities. The yield of DSBs after proton irradiation was found to rise continuously with increasing LET up to about 20 DSBs per Gbp and Gy, corresponding to an RBE up to 2.2. About half of this increase resulted from a higher yield of DSB clusters associated with small fragments below 10 kbp. Exclusion of experimentally unresolved multiple DSBs reduced the maximum DSB yield by 30% and shifted it to an LET of about 40 keV/microm. Simulated fragment size distributions deviated significantly from random breakage distributions over the whole size range after irradiation with protons with an LET above 10 keV/microm. Determination of DSB yields using equations derived for random breakage resulted in an underestimation by up to 20%. The inclusion of background fragments had only a minor influence on the distribution of the DNA fragments induced by radiation. Despite limited numerical agreement, the simulations reproduced the trends in proton-induced DNA DSBs and fragment induction found in recent experiments.

DNA↗

Multistage models and the incidence of cancer in the cohort of atomic bomb survivors.

The analyses in this paper show that a number of biologically based models describe cancer incidence among the A-bomb survivors equally well. However, these different models can predict very different temporal patterns of risk after irradiation. No evidence was found to support the previous claim of Pierce and Mendelsohn that excess cancer risks for the solid tumors depend only upon attained age and not on age at exposure or time since exposure. Although the A-bomb survivor cohort is the largest epidemiological data set for the study of radiation and cancer, it is not large enough to discriminate among various possible carcinogenic mechanisms. Unfortunately for hypothesis generation, the data appear to be consistent with a number of different mechanistic interpretations of the role of radiation in carcinogenesis.

Adult↗