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BIOPHYSICICAL MODELS FOR THE EFFECTIVENESS OF DIFFERENT RADIATIONS

Objective

This project involves experimental and theoretical research towards a better understanding of the biological radiation actions of different radiation fields, with particular emphasis on low doses and low dose rates. It aims at an improvement of our present knowledge on somatic and genetic radiation risks of man and to help develop radiation protection instrumentation to measure the characteristic properties with regard to these endpoints in mixed radiation fields. In addition, the combined action of radiation and chemicals (also of those prevalent in the environment) will be investigated on a mechanistic level.
Objectives of the project include calculation of secondary electrons produced in a water molecule and in a water cluster by proton and electron impact to investigate the influence of physical state on double differential ionization cross sections, testing of the geometry routines simulating a lymphocyte and calculation of single strand breaks (SSB), double strand breaks (DSB) and fields of dicentric chromosomes using simple models of deoxyribonucleic acid (DNA) interaction.

A set of calculations of the double and single differential cross sections for secondary electron emission as a function of angle and secondary electron energy have been completed for the case of proton impact on a water molecule and a cluster of water molecules using methods developed for electron impact. These cross sections have been integrated to yield the total cross section as a function of incident energy and energy loss per unit path length. An emperical model for electron cross sections for secondary electron emission from water has been developed and extended into the relativistic energy range. necessary analytic formulae have been derived and the model has been written into the particle tracks (PARTRAC) Monte Carlo computer code for electrons. PARTRAC was developed to include modelling of the induction of primary and secondary lesions and was applied to simulate radiation effects on human lymphocytes induced by different photon radiation qualities. For this purpose a human T-lymphocyte was simulated. At various X-ray sources track structure calculations within a lymphocyte and its environment were performed to study DNA radiation damage. The spatial distribution of the DNA DSB which are the primary lesion for chromosome aberrations was analyzed. A dose fractioning experiment was simulated to study dose rate effects.

The Monte Carlo track structure computer code was used to compute distributions of absolute frequencies of energy deposition by electrons in small cylindrical targets in water. The results of this and previous work are being compiled in monographs which will provide an extensive and consistent database for comparison of the energy deposition properties of different radiations in cylindrical target volumes including those of dimensions similar to subcellular biological structures such as deoxyribonucleic acid (DNA), nucleosomes and chromatin fibre. The track structure code has also been used to compare the abilities of different low linear energy transfer (LET) radiations to deposit their energy in the form of low energy secondary electrons. Results indicate that low energy electrons account for about 30% to 50% of the total close imparted to a medium irradiated by conventional low LET radiation and thus they may play a dominant role in the biological consequences.

The biological consequences suggested by the theoretical studies of radiation track structure were investigated in a number of ways. An irradiator for radiobiological studies with alpha particles has been constructed. It is based on a disc of plutonium-238 and allows irradiation of thin biological samples. The irradiation has been applied to a variety of cell types including rodent fibroblasts and haemopoietic progenitor cells and human peripheral lymphocytes. Methods of confocal microscopy have been developed to measure thicknesses and areas on living cells in the monolayer cultures as irradiated.

A variety of inferences are drawn on the biologically critical features of radiation tracks from low LET and high LET radiations. A particularly important feature of tracks may be the very locally clustered ionizations - excitations that can produce complex damage to DNA and associated structures. The repairability of different types of measurable DNA damage and their possible relationship to cluster size are discussed as are the consequences of low level radiation effects due to single tracks alone.

A comparative study of track structure codes was initiated. The study concentrates on the comparison of low energy electron track simulation on liquid water and water vapour. Track structure codes were obtained from 7 institutes. 6 have codes for water vapour. Of these, 3 apply the same code to the liquid phase. 3 institutes have codes for liquid water. All of the codes tend to provide the same kind of results given the data provided but the question arises as to the comparative accuracy.

The study presents comparative code data (liquid water) as elastic cross sections, exicitation cross sections and ionization cross sections. These comparisons illustrate that the basic input data of several codes is similar but nevertheless different thus results are not necessarily comparable.

The interaction of different types of ionizing radiation was studied by application of the linear-quadratic-dose effect relationship for cell survival. This information was applied as part of the model to define the influence of other types of deoxyribonucleic acid (DNA) damaging agents on the dose effect relationship. Interaction only occurs if irradiations are given simultaneously or with minutes of each other. When the time interval is longer, interaction is reduced and ultimately disappears because of repair.

Cell survival was studied using ultraviolet (UV) radiation of 2 wavelengths. Further experiments are planned.

A model based on previous work was applied to described radiation induced malignancy. The model assumes that malignancy behaves as a recessive genetic character which can be suppressed by a normalchromosome. Radiation is assumed to react by eliminating the normal suppressive gene in a cancer cell. The model logically explains these processes and the role of radiation in malignancy can be explained. The model was used to analyze lung tumors in mice and rats after acute and chronic irradiation with different types of ionizing radiation. The results show good fits of the model with experimental tumor incidence. The model explains the age dependence of the sensitivity of the animals to radiation, dose effect relationships for different radiation types, time incidence relationships and age dependence of radiation sensitivity.
This goal shall be reached by the development of new models based on:
the improvement of biophysical track structure calculations for relevant radiation fields (photons, neutrons, electrons, ions) in particular by introducing structured cell geometry, condensed state cross sections, time dependency, and chemical and biological reactions; various codes of other authors will be compared in critical bench mark calculations;
the analysis of such physical to chemical to biological track structures will be improved using new cluster algorithms and by testing biophysical models which will be developed;
selective radiation biological experiments with soft X-rays and UV-photons will be performed, as well as with alpha-particles and gamma-rays; the biological systems will include appropriate transformational and inactivation assays, etc.

The usefulness of a better understanding of radiation effects on members of the public has often been described in the radiation protection literature. This understanding is necessary also to improve the protection of workers and the public in the ALARA-sense of the IRCP, where overestimations of radiation risks might lead, for example, to a not optimum allocation of large resources.

Collaboration is foreseen with other projects working on the improvements of dosimeters and on biological radiation effects.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

GSF - FORSCHUNGSZENTRUM FUER UMWELT UND GESUNDHEIT GMBH
Address
Ingolstaedter Landstrasse 1
85764 Neuherberg
Germany

Participants (3)

ASSOCIATION POUR LE DEVELOPPEMENT DE LA PHYSIQUE ATOMIQUE
France
Address
Route De Narbonne 118
31062 Toulouse
Medical Research Council (MRC)
United Kingdom
Address
20 Park Crescent
W1N 4AL London
NATIONAL INSTITUTE OF PUBLIC HEALTH AND ENVIRONMENT
Netherlands
Address
9,Antonie Van Leeuwenhoeklaan 9
3720 BA Bilthoven