Objective
The objective is to elucidate the mechanisms by which environmental chemicals induce aneuploidy and to refine and validate assay systems capable of detecting aneugenic chemicals.
Studies indicate that lower eukaryotic systems such as those which make use of fungal cultures are not predictive for the activity of aneugenic chemicals in higher organisms. Thus, the project focuses upon the use of cell systems and intact rodents in the detection of and investigation of the mechanisms of action of environmental chemicals capable of inducing numerical chromosome changes which are of health significance to man. The major step to date was the publication of a volume of the journal Mutation Research (287(1)) in which the collaborators completed their comparative analysis of a variety of test systems using a standard set of test chemicals. This study revealed major limitations in the specificity and sensitivity of current methods and refocused the current work. Recent significant advances include: the identification of the aneugenic activity of chlorinated solvents and N-alcohols and the characterisation of the role of specific metabolic enzymes in their aneugenic activity;
comparative analysis of aneugenic activity in somatic and germ cells and the identification of a number of germ cell specific aneugens;
development and application of specific chromosome in situ hybridisation probes for the detection of aneuploidy in the rat, mouse and humans;
development of the in vitro micronucleus assay as a methodology for the detection of chemical aneugens;
characterisation of the potential aneugens to induce cell transformation as a model of chemical carcinogenesis;
molecular mechanisms of the induction of aneuploidy by spindle inhibitors.
Previous studies indicate that lower eukaryotic systems, such as those which make use of fungal cultures, are not predictive for the activity of aneugenic chemicals in higher organisms. Thus, the project focuses upon the use of cell systems and intact rodents in the detection and investigation of the mechanisms of action of environmental chemicals capable of inducing numerical chromosome changes with health significance to man.
The project involves the following work.
Identification of the cellular targets in the mammalian cells of significance in the interaction of aneugenic chemicals and the relative role of damage to such targets in induced aneuploidy.
Determination of the role of cellular and organ specific metabolism in the interaction of environmental chemicals with cellular targets of relevance.
The refinement of protocols for the detection of induced aneuploidy in cultured mammalian cells with particular focus upon the micronucleus and chromosome couting techniques. Emphasis is placed upon the development of molecular probes for the analysis of cell preparations.
The mechanisms of action and relative activities of aneugenic chemicals in both germ cells and somatic tissue will be analysed using intact rodents. Research is undertaken to determine the potential value of transgenic animals in the detection of induced aneuploidy in specific rodent tissues.
The range of chemicals evaluated in potential aneuploidy test systems is being expanded with the aim of classifying the particular chemical classes capable of interacting with relevant cellular targets.
The role of aneugenic chemicals in the progressive stages of tumour development is determined in the cell transformation assay.
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 mutation
- natural sciences earth and related environmental sciences environmental sciences pollution
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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.
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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
SA2 8PP Swansea
United Kingdom
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.