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ASSESSMENT OF THE MUTAGENIC AND CARCINOGENIC RISKS OF CHEMICALS.

Objective

1) TO RELATE BIOLOGICAL CONSEQUENCES OF CHEMICAL MUTAGENS TO THE EXTENT AND SITE OF REACTION BETWEEN THE MUTAGENS AND DNA.
2) DEVELOPMENT AND VALIDATION OF METHODS TO IDENTIFY NON-GENOTOXIC CARCINOGENS.
3) DEVELOPMENT AND VALIDATION OF ASSAYS TO EVALUATE CHEMICALS CAPABLE OF INDUCING GENOMIC MUTATIONS.
The induction of micronuclei by the alkylating agent N-methyl-N-nitrosourea (MNU) was studied in cell lines with different capacities to repair O6-methylguanine (O6meG). The frequency of micronuclei induced by MNU was higher in the O6meG-DNA-methyltransferase (MT) deficient than in the MT-proficient cell line, suggesting a role for O6meG in the induction of micronuclei.
1) THE INSTITUTE CONTINUES ITS PARTICIPATION IN THE MOLECULAR DOSIMETRY PROJECT: CHINESE HAMSTER CELLS AND HUMAN LYMPHOCYTES ARE TREATED WITH THE TEST CHEMICALS AND USED TO
I) MEASURE DNA ALKYLATION AT SPECIFIC SITES AND
II) MEASURE GENE MUTATION AND CHROMOSOME ABERRATIONS.

2) DNA AND PROTEIN CHANGES ASSOCIATED WITH THE ACTION OF EPIGENETIC CHEMICALS; SELECTED PROMOTING AGENTS FOR THE RAT LIVER MODEL OF CARCINOGENESIS; FOR THE MOUSE SKIN MODEL AND FOR COLON CARCINOGENESIS ARE STUDIED BY AN INTEGRATED PHYSICOCHEMICAL APPROACH INCLUDING ELECTRON MICROSCOPIC, MICROCALORIMETRIC AND ELECTROPHORETIC METHODS.

3). MICRONUCLEI FORMATION IN HUMAN LYMPHOCYTES; MICRONUCLEI INDUCED IN HUMAN LYMPHOCYTES BY ANEUPLOIDY CAUSING AGENTS ARE SEPARATED AND FUSED WITH MOUSE OR HUMAN CELLS. FLOW CYTOMETRY IS USED TO SEPARATE MICRONUCLEI ACCORDING TO SIZE, TO TEST THE RELATIVE CONTRIBUTIONS OF CHROMOSOME BREAKAGE AND CHROMOSOME LOSS.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

INSTITUTO NAZIONALE PER LA RICERCA SUL CANCRO
Address
Largo Rosanna Benzi 10
16132 Genova
Italy