Objective
Efforts have been made to improve experimental, computational, and system analytical studies the present knowledge on the form of the relevant biological dose-time-effect curves especially in the low dose regime of radiation protection ant its dependency on the dose rate, fractionation, type of radiation (X, gamma, alpha, beta, neutrons and mixed fields), and on the influence of environmental factors. The scientific approach to develop an appropriate integral mechanistic model for radiation carcinogenesis was differentiated into the development of several models for the different levels of biological complexity, namely for the production of primary and secondary physical and early chemical changes in the DNA, for the formation of mutations (e.g. HPRT-) and chromosome aberrations, the induction of late somatic effects in experimental animals and man by such early effects including intercomparison with the mechanistic action of UV-light. Particular emphasis was given to the improvement of track structure simulations codes, the study of biochemical reactions, and modelling of the induction of cancer by alpha emitters.
THIS PROJECT PLANS TO CONTINUE THE WORK OF THIS GROUP TOWARDS THE LONG TERM GOAL OF THE DEVELOPMENT OF QUANTITATIVE,VALIDATED,MECHANISTIC MODELS FOR THE INDUCTION OF SOMATIC LATE EFFECTS IN MAN BY LOW DOSES AND DOSE RATES OF DIFFERENT QUALITIES OF IONIZING RADIATION.
IN THIS PROPOSAL EXPERIMENTAL, COMPUTATIONAL AND SYSTEMS ANALYTICAL WORK IS FORESEEN TO IMPROVE THE PRESENT KNOWLEDGE ON THE SHAPE OF THE DOSE-TIME-EFFECT CURVES ESPECIALLY IN THE LOW DOSE REGIME OF RADIATION PROTECTION AND ITS DEPENDENCE ON THE TIME SCHEDULE OF DOSE DELIVERY, THE TYPE OF RADIATION AND ON THE INFLUENCE OF ENVIRONMENTAL FACTORS. THE SCIENTIFIC APPROACH TO DEVELOP SUCH AN INTEGRAL MECHANISTIC (I.E. NOT EMPIRICAL) MODEL FOR RADIATION CARCINOGENESIS IS STRUCTURED IN THIS PROJECT INTO THE DEVELOPMENT OF SEPARATE,SERIAL MODELS FOR THE DIFFERENT LEVELS OF BIOLOGICAL COMPLEXITY : A) THE INDUCTION BY RADIATION ACTION OF EARLY PHYSICAL AND CHEMICAL CHANGES IN THE DNA (BY TERRISSOL, O'NEILL, V. SONNTAG),
B) THE SUBSEQUENT FORMATION OF MUTATIONS (E.G. HPRT-) AND CHROMOSOME ABERRATIONS (PARETZKE, GOODHEAD),
C) THE INDUCTION OF CELLULAR CHANGES AND LATE SOMATIC EFFECTS IN EXPERIMENTAL ANIMALS AND MAN BY SUCH EARLY CELL EFFECTS INCLUDING INTERCOMPARISON WITH THE MECHANISTIC ACTION OF UV-LIGHT (LEENHOUTS, PARETZKE). DURING THE PREVIOUS CONTRACT PERIOD MAINLY LITERATURE WORK, DEVELOPMENT OF NEW COMPUTER CODES AND SELECTED EXPERIMENTS WERE PERFORMED. PRELIMINARY RESULTS SHOWED THE GENERAL USEFULNESS OF THE TOOLS AND CONCEPTS DEVELOPED.THE WORK OF THE PRESENT PROPOSAL AIMS AT USING THESE TOOLS IN THE DEVELOPMENT OF MECHANISTIC MODELS FOR THE VARIOUS LEVELS INDICATED ABOVE AND THE EARLY BIOCHEMICAL STAGE OF THE EFFECTS. TO THIS PURPOSE THE PRECIOUS RESEARCH GROUP HAS NOW BEEN ENLARGED BY TWO RADIATION CHEMISTS.
PARTICULAR EMPHASIS WILL BE GIVEN TO THE MECHANISTIC INTERPRETATION OF THE HPRT- MUTATION AND THE INDUCTION OF LUNG TUMORS BY ALPHA EMITTERS.CLOSE CONTACTS ARE PLANNED WITH GROUPS OF EURADOS IMPROVING MEASUREMENT TECHNIQUES FOR RISK RELATED QUANTITIES, WITH EULAP, WITH GROUPS IMPROVING THE BIOLOGICAL, CHEMICAL AND PHYSICAL DATA BASES AND WITH SIMILAR RESEARCH ACTIVITIES IN THE USA.
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Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
85764 OBERSCHLEISSHEIM
Germany