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COOPERATION BETWEEN RADIATION AND ONCOGENES IN MALIGNANT TRANSFORMATION OF MAMMALIAN CELLS

Objective


Investigations have included molecular analysis of the transient conditional response induced by radiation in normal human fibroblasts.

The objectives were: to obtain a quantitative in-vitro cell transformation system using human keratinocytes to assess the risks in humans from exposure to ionising radiation; to determine whether radiation transformed human cells are a preferential target for the replication of autonomous paroviruses or are preferentially killed by them. We dealt with the molecular analysis of the transient conditional response induced by radiation in normal human fibroblasts.
THE INCIDENCE OF MALIGNANT TRANSFORMATION FOLLOWING EXPOSURE TO CARCINIGENS DEPENDS ON SEVERAL CELLULAR PARAMETERS WHICH MAY VARY AMONG DIFFERENT CELLS AND/OR INDIVIDUALS. THE IDENTIFICATION OF THESE PARAMETERS CONDITIONING CELL SUSCEPTIBILITY TO TRANSFORMATION IS IMPORTANT NOT ONLY FROM A FUNDAMENTAL POINT OF VIEW BUT ALSO FOR RISK ASSESSMENT. THE GENERAL GOAL OF THIS PROJECT IS TO SET UP HUMAN CELL CULTURES AS IN VITRO MODEL SYSTEMS FOR THE DETECTION OF ACQUIRED OR INHERITED CELLULAR CHANGES COOPERATING WITH IONIZING RADIATION FOR THE INDUCTION OF MALIGNANT TRANSFORMATION ARE POORLY UNDERSTOOD.
THIS IS DUE, IN PART, TO DIFFICULTIES IN QUANTIFYING IN-VITRO TRANSFORMATION WHICH CULTURES OF HUMAN FIBROBLASTS.
ON THE BASIS OF DATA REPORTED FOR OTHER CARCINOGENS, IT IS PROPOSED IN SECTION 1 OF THIS PROJECT TO DEVELOP AN ALTERNATIVE ASSAY FOR TRANSFORMATION AFTER IONIZING IRRADIATION, USING CULTURES OF HUMAN EPITHELIAL CELLS.
THIS AND MORE CONVENTIONAL ASSAYS WILL BE APPLIED TO THE SEARCH OF CELLULAR DETERMINANTS OF TRANSFORMATION, ACCORDING TO A THREE-POINT STRATEGY.
SECTION 2.-SYNERGISTIC EFFECTS BETWEEN RADIATION, ONCOGENES AND TUMOUR PROMOTERS.
SECTION 3.-CELLULAR RESPONSEES TO RADIATION ASSOCIATED WITH HUMAN CANCER0PRONE CONDITIONS.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITE LIBRE DE BRUXELLES
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Av. F.d. Roosevelt,50
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Belgium