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GENETIC EFFECTS OF ENVIRONMENTAL CHEMICALS

Objectif

1) STUDY OF MOLECULAR INTERACTIONS OF ENVIRONMENTAL MUTAGENS AND CARCINOGENS AT DNA LEVEL.
2) RELATE BIOLOGICAL CONSEQUENCES OF CHEMICAL MUTAGENS TO THE EXTENT AND SITE OF REACTION BETWEEN THE MUTAGENS AND DNA.
3) DEVELOPMENT AND VALIDATION OF METHODS TO IDENTIFY NON-GENOTOXIC CARCINOGENS.
4) DEVELOPMENT AND VALIDATION OF ASSAYS TO EVALUATE CHEMICALS CAPABLE OF INDUCING GENOMIC MUTATIONS.
A range of alkylating agents were evaluated in positive assays for chromosome malsegregation in A. nidulans. Disturbance of chromosome segregation was found to be the primary genetic event for a range of alkylating agents. However, a number of the agents also induced cross-overs (and terminal deletions), hence additional assays are required before the origin of the observed segregants can be determined.
1) THE USE OF A SHUTTLE VECTOR AS PROBE FOR INVESTIGATING MUTAGENESIS BY CHEMICAL CARCINOGEN ADDUCTS IN MAMMALIAN CELLS; RECOMBINENT GENOMES CONTAINING SPECIFIC LESIONS AT A SPECIFIC SITE ARE CONSTRUCTED.
PREMUTAGENIC DNA LESIONS ARE BUILT AT KNOW POSITIONS IN THE APPROPRIATE SHUTTLE VECTORS TO PROBE WHAT HAPPENS IN MAMMALIAN CELLS WHEN DNA POLYMERASES AND REPAIR ENSYMES ENCOUNTER THESE CARCINOGEN ADDUCTS.

2) THE RESEARCH TEAM WILL CONTINUE TO PARTICIPATE IN THE MOLECULAR EMPHASIS ON THE MAMMALIAN CELL LINE CHO.

3) ONCOGENE EXPRESSION IN TRANSFORMED CELLS:-
THE MECHANISMS OF ACTION OF TUMOUR PROMOTORS ON DIFFERENT TYPES OF ONCOGENES ARE STUDIED BY EXAMINING THE PROLIFERATION OF CERTAIN NORMAL CELLS (E.G.C3H1OT1/2)IN "EXCESS".

4) THE ANEUPLOIDIZING ACTIVITY OF MODEL COMPOUNDS ARE STUDIED IN A NIDULANS MITOTIC CELLS AND BY CYTOGENIC ANALYSIS IN MOUSE BONE MARROW CELLS AND SECONDARY SPERMATOCYTES.

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Régime de financement

CSC - Cost-sharing contracts

Coordinateur

ISTITUTO SUPERIORE DI SANITA
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Viale Regina Elena 299
00161 ROMA
Italie

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