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MOLECULAR ANALYSIS OF MUTAGENESIS IN MAMMALIAN CELLS TREATED BY RADIATIONS AND CHEMICAL CARCINOGENS

Cel

THE GENERAL THEME OF THIS RESEARCH PROPOSAL IS THE STUDY OF RELATIONSHIPS BETWEEN THE EXISTENCE OF DNA LESIONS INDUCED BY RADIATIONS OR CARCINOGENS AND THEIR CONSEQUENCES ON THE INITIATION OF CARCINOGENESIS.
THE DNA REPAIR PROCESSES ARE VERY IMPORTANT IN THIS RESPECT SINCE A MUTATION EVENT COULD EITHER COME FROM AN UNREPAIRED LESION OR A LESION REPAIRED BY AN ERROR-PRONE PROCESS. THIS LATTER PROCESS, CALLED SOS REPAIR IN BACTERIA, HAS BEEN SHOWN TO OCCUR IN SPECIFIC CONDITIONS IN MAMMALIAN CELLS.

EXOGENEOUS DNA IS VERY USEFUL TO ANALYSE INDUCOBLE SOS FUNCTIONS SINCE IT PERMITS ONE TO DISCRIMINATE BETWEEN THE "INDUCING" TREATMENT CARRIED OUT ON THE CELL, AND THE DNA LESIONS TO BE REPAIRED. ANIMAL DNA VIRUSES OR SHUTTLE VECTORS CAN BE USED AS BIOLOGICAL PROBES FOR STUDYING SOS REPAIR PROCESSES IN EUKARYOTES.
CELLS ARE FIRST TREATED BY UV-RADIATION OR CHEMICAL CARCINOGEN, THEN INFECTED WITH VIRUS PRE-IRRADIATED IN VITRO. THE WAY IRRADIATED VIRUS IS REPAIRED OR MUTATED IN TREATED CELLS CAN TELL US HOW SOS REPAIR WORKS. SUCH EXPERIMENTS ARE CARRIED OUT WITH MONKEY KIDNEY CELLS OR HUMAN CELLS AND SIMIAN VIRUS 40 (SV40). NUMEROUS MUTANTS OF SV40 BEING WELL CHARACTERIZED, THE VIRUS PERMITS THE STUDY OF MUTAGENIC PROPERTIES OF SOS REPAIR.
IN A COMPLEMENTARY WAY SEVERAL PROCESSES LINKED TO DNA REPAIR WILL BE ANALYSED EITHER BY STUDYING SOME ENZYMES INVOLVED IN THE REPAIR PATHWAY SUCH AS DNA LIGASES.
Characterisation, at the molecular level, of the type of mutation induced by ultraviolet (UV) light or by different chemical carcinogens in mammalian cells has been achieved. Specific genes have been used as probes for mutagenesis, oncogenesis in xeroderma pigmentosum patients, and for characterisation of deoxyribonucleic acid (DNA) ligase activities.

Studies are being carried out on the use of specific genes as probes for mutagenesis and oncogenesis in xeroderma pigmentosum (XP) patients, and on the characterisation of deoxyribonucleic acid (DNA) ligase activities in mammalian cells.
1.-USE OF SPECIFIC GENES AS PROBES FOR MUTAGENESIS.

2.-ONCOGENESIS IN XERODERMA PIGMENTOSUM PATIENTS

3.-CHARACTERIZATION OF DNA LIGASE ACTIVITIES.

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Koordynator

Centre National de la Recherche Scientifique (CNRS)
Wkład UE
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Adres
15 Quai Anatole France
75700 Paris
Francja

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