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EXPERIMENTAL APPROACH OF ABSOLUTE AND RELATIVE RISK CONCEPTS IN RADIOINDUCED CANCERS. ROLE OF COMBINED EFFECTS

Objetivo

APPLICATION OF THE ABSOLUTE RISK CONCEPT IMPLIES THAT THE INCREASE IN CANCER IN A CERTAIN POPULATION IS CONSTANT AND INDEPENDENT OF AGE; REGARDLESS WHICH AGE RANGE IS CONSIDERED, THE EFFECT SHOULD BE THE SAME.
RELATIVE RISKS IMPLY THAT THE SPONTANEOUS CANCER INCIDENCE IS MULTIPLIED WITH A CERTAIN FACTOR. SINCE SPONTANEOUS CANCER INCIDENCE DEPENDS ON AGE, THE EXCESS INDUCED CANCER IS ALSO DEPENDENT ON AGE.
WORKING HYPOTHESES:
THE ACCELERATION OF THE APPEARANCE OF SPONTANEOUS TUMOURS IN A GROUP OF ANIMALS EXPOSED TO RADIATION IS AS MUCH PART OF THE CARCINOGENIC PROCESS AS THE INDUCTION OF TUMOURS IN A TISSUE WHICH NORMALLY IN A CONTROL GROUP SHOWS NO OR FEW SPONTANEOUS TUMOURS.
ACCELERATION AND INITIATION OF TUMOURS ARE INTERRELATED BY A QUANTITATIVE RELATION WHICH CAN BE EXPERIMENTALLY DETERMINED IN RODENTS FOR FATAL AS WELL AS FOR INCIDENTAL TUMOURS.
THIS STUDY INTENDS TO VERIFY THESE ASSUMPTIONS IN CONTROL RATS AND IN NEUTRON OR GAMMA IRRADIATED RATS. THE COMBINED EFFECT OF CARCINOGENIC AGENTS AND PROMOTERS WILL ALSO BE CHARACTERIZED BY A QUANTITATIVE RELATION IN AGREEMENT WITH THE DIFFERENT HYPOTHESES CORRESPONDING TO THE INITIATING AND PROMOTING MECHANISMS. THE STUDY ATTEMPTS TO VERIFY WHETHER THE INITIATION-PROMOTION SEQUENCE IS OF MULTIPLICATIVE CHARACTER.
The underlying mechanisms which produce curves of comparable form for the 3 radiation types help in the calculation of relative biological effectiveness (RBE). The RBE for neutrons in comparison with gamma radiation from cobalt 60 is, both at lower doses and for all cancers, of the order of 50. For radon the RBE (WLM cCy gamma) is of the order of 5 for lower doses and pulmonary cancer.
EXPERIMENTAL PROCEDURE:
EXPERIMENTAL DATA ALREADY IN PART AVAILABLE ALLOW THE MATHEMATICAL ANALYSIS OF A GROUP OF 600 MALE CONTROL SPRAGUE-DAWLEY RATS AND OF 2 GROUPS OF MORE THAN 1000 RATS IRRADIATED WITH NEUTRONS OR GAMMA RAYS. THE RESULTS FOR THE DIFFERENT RADIATION-INDUCED CANCERS WILL BE EXPRESSED AS ABSOLUTE OR RELATIVE RISKS.
THE INITIATION EVENTS IS REPRESENTED BY IRRADIATION SEVERAL FACTORS OF WHICH ARE VARIED: DOSE, DOSE RATE AND QUALITY OF RADIATION.
THE STUDY OF PROMOTING FACTORS INVOLVES DIFFERENT AGENTS SUCH AS CHEMICAL SUBSTANCES (BENZOFLAVONE) WHICH HAVE A SPECIFIC ACTION ON THE BRONCHIAL CELLS IN LUNG, DUSTS (HEMATITE, BERYLLIUM) OR FIBRES (ASBESTOS, QUARTZ, GLASS FIBRES...) WITH INITIATION BY INHALATION OF RADON. THREE YEARS WILL BE REQUIRED TO STUDY THE FACTOR "PROMOTION", AND THIS WILL ALSO ALLOW TO COMPLETE AND EVALUATE THE STUDY ON RADIATION.
DURING THE FIRST YEAR, FOLLOWING INHALATION OF RADON BY 150 RATS INTRATRACHEAL INJECTION WILL BE COMPARED WITH THAT IN A GROUP OF 100 RATS TREATED WITH BENZOFLAVONE. A STUDY OF THE EFFECTS OF DIFFERENT DOSES OF PROMOTERS AFTER IRRADIATION WITH VARIOUS DOSES OF NEUTRONS AND GAMMA RADIATION WILL FOLLOW AND IT WILL BE ATTEMPTED TO DEFINE THE THRESHOLD DOSES.
DURING THE SECOND YEAR, THE PATHOLOGICAL ANALYSIS OF THE DEAD RATS WILL BE CARRIED OUT, AND THE ACTION OF DIFFERENT INJECTED FIBERS AND DUSTS WILL BE COMPARED.
DURING THE THIRD YEAR, THE DATA ON PROMOTION FOLLOWING NEUTRON OR GAMMA IRRADIATION WILL BE ANANLYSED, AND THE COMBINED EFFECTS OF DIFFERENT DOSES OF INITIATORS AND PROMOTORS ON THE APPEARANCE OF LUNG CANCER WILL BE STUDIED.

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CSC - Cost-sharing contracts

Coordinador

Commissariat à l'Energie Atomique (CEA)
Aportación de la UE
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Dirección
Centre d'Études de Fontenay-aux-Roses
92265 Fontenay-aux-Roses
Francia

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