Objective
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 TO NEW GROUP OF MUTAGENS AND ADDITIONAL BIOLOGICAL ASSAYS TO EVALUATE CHEMICALS CAPABLE OF INDUCING GENOMIC MUTATIONS.
5) TO DEVELOP TEST METHODS WHICH REPLACE OR REDUCE THE USE OF EXPERIMENTAL VERTEBRATE ANIMALS.
The genetic basis of mutations induced by environmental chemicals was investigated. All the ENU-induced mutations observed were due to base pair changes. Twenty nine nucleotide substitutions were found in total and of these 79% were transition type mutations and 21% were transversion type mutations. In all cases the GC to AT transition predominated and the same was true for 9 mosaic mutations isolated in the F2 generation.
1) NEW METHODS APPLIED TO MONITOR DNA DAMAGE AND TO EVALUATE BIOLOGICAL EFFECTS: THE MECHANISMS OF MUTAGENESIS ARE INVESTIGATED, WITH PARTICULAR EMPHASIS ON DNA REPAIR OF ALKYLATION PRODUCTS; COMPARATIVE STUDIES OF MULTIPLE AND SPECIFIC LOCUS MUTATIONS IN DROSOPHILA AND VALIDATION OF THE SOMATIC MUTATION ASSAY. ANALYSIS OF MUTATIONAL CHANGE AT DNA LEVEL. USE OF HOST MEDIATED ASSAY TO CHARACTERIZE ORGAN SPECIFIC METABOLITES
2) THE ONGOING PROGRAMME IS EXTENDED TO NEW GROUPS OF MUTAGENS AND ADDITIONAL BIOLOGICAL ASSAYS. DOSIMETRY STUDIES ARE EXTENDED TO INCLUDE THOSE AT SINGLE CELL LEVEL USING MONOCLONAL ANTIBODIES AGAINST SPECIFIC ADDUCTS. EPIDEMIOLOGICAL STUDIES ARE UNDERTAKEN USING BOTH MUTATIONS AT THE HPRT LOCUS IN LYMPHOCYTES DETECTED BY CLONING AND HEMOGLOBIN MUTATIONS USING ANTIBODIES AGAINST SPECIFIC POINT MUTATIONS OR DELETIONS
3) THE EFFECTS OF NON-GENOTOXIC CARCINOGENS ON REPLICATIONAL FIDELITY OF DNA SYNTHESIS WILL BE EXAMINED
4) THE TECHNIQUE DEVELOPED DETECT NON-DISJUNCTION EVENTS IN-VITRO, STANDARDIZED USING PRIMARY EMBRYONIC FIBROBLASTS FROM CHINESE HAMSTER IS USED TO EVALUATE SELECTED MODEL COMPOUNDS
5) DETERMINATION OF THE EXTENT TO WHICH HUMAN ERYTHROCYTES AND CELL- HOMOGENATES FROM PLANT MATERIAL CAN BE USED FOR THE ACTIVATION OF SOME CLASSES OF PROMUTAGENS.
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 biological sciences genetics mutation
- natural sciences earth and related environmental sciences environmental sciences pollution
- natural sciences biological sciences genetics nucleotides
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Coordinator
2311 EZ LEIDEN
Netherlands
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