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Development of assays for the detection and prediction of co- and antimutagenic constituents in food with cells of human origin
HEPADNA

Contract number : QLK1-1999-00810
Contract type : Shared Cost Project
Total cost : € 1.069.386
EC contribution : € 898.019
Starting date : 1/02/2000
Duration : 36 Months
Scientific Officer : Alkmini Katsada
Project website : not yet available
Coordinator
Prof. Dr Firouz Darroudi
Leiden University Medical Centre
Department of Radiation Genetics and Chemical Mutagenesis
Wassenaarseweg 72
2333AL Leiden
The Netherlands
Tel.: +31-71-5276168
Fax: +31 71 5276173
E-mail: f.darroudi @ lumc.nl
Background

It is well documented that diet and the existing food contaminants play crucial roles in the aetiology of cancer in humans. In order to perform a reliable risk assessment for human in the present proposal we plan to develop and validate new assays using human hepatoma and hepatocyte cell systems. DNA-damage,-repair, and biological consequences will be studied. Furthermore, the key role of the specific enzymes in mutagenicity will be determined. An automated scoring analysis of micronuclei will be used to analyse a larger number of chemicals, and with the help of a computer automated structure evaluation methodology, attempts will be made to detect structure activity relationship of different chemicals, in order to detect/predict the hazard/protective effect of active compounds in the food matrix.

Objectives

A number of epidemiological studies indicated that the composition of the diet plays a major role in the aetiology of cancer in humans and it has been estimated that 40-70% of the cancer incidence in humans is due to nutritional factors.

So far, the main approaches which enable detection of mutagens, co- and anti-mutagens are in vivo models with laboratory animals, but in general they are relatively time consuming and costly, and the requirement of large animal numbers urges against their use in screening trials. Furthermore, the outcomes may not be true representatives of human situations in vivo.

The overall aim of the project is to investigate the effect of dietary constituents and contamination on the genotoxic effects of representatives of major groups of food derived carcinogens in cells of human origin. To obtain reliable information which of the food constituents may enhance or reduce the health risks of humans.

Techniques will be developed and applied using human derived liver cells that reflect the activation/detoxification of genotoxic carcinogens better than other indicator cells that are currently being used. Therefore, have an increased predictive value for the identification of mutagens, co- and anti-mutagenic constituents of human foods.

(expected) Results and achievements
  • To increase our knowledge for the mutagenic, co- and anti-mutagenic potential of human food constituents.
  • To define the mode of action, DNA damage induction, repair and biological consequences.
  • To detect and elucidate the role of different enzymes involved and responsible for mutagenic, co- and anti-mutagenic potential of food constituents.
  • To detect and may predict chemical structures that are of particular importance for the protective/hazardous properties of the various classes of food constituents
  • Ultimately improve human health: This project is designed to provide the scientific basis for the development of improved food products and is targeted on the provision of health benefits to consumers.
  • Identification of desirable and optimal levels of mutagens, co- and anti-mutagens in human food constituents, will enable advice, strategies and recommendation for healthy diets to be more effectively targeted nationally and through European channels.

Partners

Institute for Cancer Research
Environmental Toxicology Group
Borschkegasse 8A
1090 Vienna
Austria
Ruprecht-Karls-Universität Heidelberg
Fakultät für Klinische Medizin Mannheim
Institut für Medizinische Mikrobiologie und Hygiene
Theodor-Kutzer-Ufer 1-3
PO Box 100023
68167 Mannheim
Germany
Fraunhofer-Institut für Toxikologie und Aerosolforschung
Nikolai-Fuchs-Straße 1
30625 Hannover
Germany
INRA Jouy-en-Josas
Unité d'Ecologie et de Physiologie du Système Digestif
Domaine de Vilvert
Bâtiment 440
78352 Jouy En Josas
France


Fifth Framework Programme

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Last update

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23-09-2003



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