Objective
ETHENO (e)-BRIDGED ADDUCTS IN DNA ARE FORMED BY A NUMBER OF ENVIRONMENTAL AND ENDOGENOUSLY PRODUCED GENOTOXINS, SOME WITH WIDESPREAD HUMAN EXPOSURE. TO ASSESS THE ROLE OF THESE PROMUTAGENIC DNA LESIONS IN HUMAN CARCINOGENESIS, FOUR KEY COMPOUNDS REPRESENTATIVE OF THIS CLASS (VINYL CHLORIDE, URETHANE, VINYL CARBAMATE AND ITS EPOXIDE) WILL BE INVESTIGATED AS FOLLOWS:
(A) QUANTIFICATION OF e-ADDUCTS IN DNA OF RODENT TISSUES, MAMMALIAN CELLS AND DROSOPHILA, BY THE MOST SENSITIVE METHOD AVAILABLE (RECENTLY DEVELOPED AT IARC), AND MEASUREMENT OF PERSISTENCE AND REPAIR OF e-ADDUCTS IN EXCISION REPAIR-PROFICIENT AND DEFICIENT CHO CELL LINES AND DROSOPHILA.
(B) CHARACTERIZATION OF MUTATIONAL SPECTRA IN THREE REPORTER GENES: HPRT (CHO CELLS), VERMILION (DROSOPHILA) AND LACI (BIG BLUE TRANSGENIC MICE). (C) DETERMINATION OF GENETIC ACTIVITY PROFILES (MUTATIONS,
CLASTOGENICITY AND HYPERMUTABILITY) IN CHO CELLS AND DROSOPHILA AND OF DNA DAMAGE IN TRANSGENIC MICE (COMET ASSAY). - - - - -
(D) ESTIMATION OF TD5O VALUES AND MEASUREMENT OF COVALENT BINDING INDICES (CBI) IN RODENTS FOR A LARGER SERIES OF e-ADDUCT FORMING AGENTS. (E) FINALLY, GENETIC, REPAIR AND DNA BINDING DATA WILL BE USED TO CLASSIFY THESE AGENTS ACCORDING TO THEIR MECHANISM OF ACTION, TO ESTABLISH QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS AND TO PREDICT CARCINOGENIC POTENCY FOR THIS CLASS OF COMPOUNDS. ALTOGETHER, THIS NOVEL APPROACH WILL CORRELATE FOR THE FIRST TIME, DNA BINDING DATA WITH ALL GENETIC ENDPOINTS IN VARIOUS SYSTEMS AND WITH TUMORIGENIC POTENCY IN RODENTS AND HUMANS. THESE DATA WILL ALSO ALLOW TO EXAMINE THE ORIGIN OF BACKGROUND LEVELS OF e-ADDUCTS IN HUMAN TISSUES AND THEIR RELEVANCE FOR CARCINOGENIC RISK ASSESSMENT.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences physical sciences astronomy planetary sciences comets
- natural sciences biological sciences genetics mutation
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
69120 HEIDELBERG
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.