Objective
The proposal will address modes of action for tumour induction in liver by the food contaminant furan, which is formed by processing of food resulting in widespread human exposure. There is uncertainty regarding the relevance of tumours induced in rodents to human risk assessment because the mechanisms are unclear. The research will address the role of DNA and protein binding of furan, oxidative DNA damage, non-genotoxic alteration of proliferation and apoptosis, cytogenetics and cytotoxicity in furan-mediated liver toxicity and carcinogenicity. A combination of in vivo and in vitro systems, analytical chemistry, cell biology and "omics" technologies will be applied. In rodents in vivo, extent and dose-dependence of covalent binding to DNA, cytogenetic changes and geno- and cytotoxicity in target cells in the liver will be addressed after oral administration of furan. In addition, the induction of oxidative DNA-modifications and mechanisms of mutations will be investigated in genetically modified rodent models. These in vivo studies will characterize the mode of action of furan and also address irreversible metaplasia, changes in cell signaling and inflammation. The interaction of these effects with possible genetic changes in liver cells including aspects of forced cell proliferation will be included. The in vivo work will be complemented by studying mode of mutation of furan and its metabolite cis-2-butene-1,4-dial in cell culture models resembling the target cells. The content of furan in food will be determined and human exposures will be assessed using probabilistic modeling. Mechanisms of formation of furan in food may open ways to reduce exposures. The results will provide data on the mode-of-action of furan induced liver carcinogenesis as a basis for a conclusive assessment of health risks in humans due to dietary exposure. Combining these findings will provide a risk/benefit analysis and a scientific basis to justify limits for human furan exposures.
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 chemical sciences analytical chemistry
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- natural sciences mathematics applied mathematics statistics and probability
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-SSP-5-A
See other projects for this call
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
WUERZBURG
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.