Objectif The objective of the project is the development of methods for assessing the genetic burden, resulting from exposure to chemical carcinogens, in the general population.The genetic burden associated with human exposure to urban air pollution is as yet unclear, although the presence of a wide variety of carcinogenic chemicals has been identified. Exposure to genotoxic carcinogens results in the formation of covalently bound adducts between the carcinogen and DNA. Many so-called 'non-genotoxic' carcinogens also damage DNA by virtue of the fact that they generate active radicals which oxidize nucleic acid bases. Measurement of adducts or oxidized DNA bases may thus be used as a monitor of carcinogen exposure. Exposure to genotoxic carcinogens may also be monitored by determination of adducts formed with proteins, such as haemoglobin.This research project is concerned predominantly with the development of novel biomonitoring approaches using adduct measurement. These methods are to be applied to biological samples collected from populations in a representative group of European cities and from Kuwaitis exposed to high levels of oil combustion pollutants as well as from populations in Northern and Southern Bohemia. A questionnaire to gather relevant information on lifestyle and environmental factors will be used. Other information to be gathered on the exposed individuals are the analysis of their metabolic phenotype (i.e. capacity to metabolise carcinogens to their active species) and of their DNA repair ability (i.e. capacity to remove genotoxic damage).The analytical procedures used to detect DNA adducts will be 32P-postlabelling, gas chromatography-mass spectrometry (GC-MS) and HPLC. 32P-postlabelling is an exceptionally sensitive technique capable of detecting carcinogen-modified bases in DNA. It is intended to make several innovations to this method, to make it more amenable for routine use. Oxidative DNA damage (8-hydroxyguanine) will be monitored using HPLC; attempts will also be made to use GC-MS to monitor other oxidized DNA bases, and adducts of genotoxic carcinogens with haemoglobin. Traditionally, lymphocyte DNA is favoured for adduct measurements. It is planned to investigate other DNA sources (e.g. placenta, oral tissues, buccal smears) which may be of greater relevance to carcinogen risk analysis.The work will result in:i) The design of novel biomonitoring methods for detecting adducts of carcinogens with DNA and protein,ii) A comparison of adduct levels in DNA from different tissues which will indicate the most appropriate tissues to use for biomonitoring purposes,iii) The establishment of baseline data for adducts levels, as a pre-requisite for epidemiological studies at the EC level. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsengineering and technologyenvironmental engineeringair pollution engineeringnatural sciencesearth and related environmental sciencesenvironmental sciencespollution Programme(s) FP3-ENV 1C - Specific research and technological development programme (EEC) in the field of the environment, 1990-1994 Thème(s) 040203 - Environment and human health Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur MEDICAL RESEARCH COUNCIL Contribution de l’UE Aucune donnée Adresse Lancaster Road University of Leicester Hodgkin Bui LE1 9HN Leicester Royaume-Uni Voir sur la carte Coût total Aucune donnée Participants (3) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire NATIONAL HELLENIC RESEARCH FOUNDATION Grèce Contribution de l’UE Aucune donnée Adresse 48,Vas. Constantinou Avenue 48 11635 ATHENS Voir sur la carte Coût total Aucune donnée UNIVERSITY OF AARHUS Danemark Contribution de l’UE Aucune donnée Adresse 180,Vennelyst Boulevard, 6 8000 AARHUS C Voir sur la carte Coût total Aucune donnée UNIVERSITY OF WALES SWANSEA Royaume-Uni Contribution de l’UE Aucune donnée Adresse Singleton Park SA2 8PP SWANSEA Voir sur la carte Coût total Aucune donnée