Objective The genetic buden associated with human exposure to urban air pollution is as yet unclear, although the presence of a wide variety of carcinogens has been identified. Exposure to genotoxic carcinogens results in the formation of covalently bound adducts between carcinogen and DNA. Many non genotoxic carcinogens also damage DNA by virtue of thefact that they generate active radicals which oxidise nucleic acid bases. Exposure to genotoxic carcinogens may also be monitored by determination of adducts formed with proteins such as haemoglobin.The research project has been concerned predominantly with the development of novel biomonitoring approaches using adduct measurement. These methods were applied to biological samples collected from populations in a representative group of European locations and from Kuwaitis exposed to high levels of oil combustion products. A questionnaire to gather relevant information on lifestyles and environmental factors was used. Other information obtained on the exposure of individuals were the analysis of their metabolic phenotype (ie capacity to metabolise carcinogens to their active species) and of their DNA repair ability.The analytical procedures used to detect DNA adducts were P32 postlabelling and gas chromatography-mass spectrometry (GC-MS). P32 postlabelling is an exceptionally sensitive technique capable of detecting carcinogen modified bases in DNA. Several innovations were made to this method to make it more amenable for routine use. Oxidative DNA damage and adducts with haemoglobin were measured using GC-MS. Traditionally, lymphocyte DNA has been favoured for adduct measurements. Other DNA sources (eg placenta, oral tissue, buccal smears) which may be of greater relavence to carcinogen risk analysis were also investigated in detail.A coordinated study is planned between 15 participants in 9 countries on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. These procedures will measure both primary events (carcinogen-adducts on DNA or protein) and secondary effects (mutation, cytogenetic damage). Adduct detection will be by 32p-postlabelling, immunochemical, HPLC or mass spectrometric methods. Although established methods will be used, considerable method development is also planned in all assays. Emphasis will be placed on populations exposed to urban pollution and in particular to the genotoxicants present in such samples that result from petrochemical combustion or processing. Blood and urine samples from individuals in urban locations from 8 countries will be collected and distributed amongst the programme's participants. Air Samples will also be collected and analysed. Populations exposed through occupational or medical sources to larger amounts of some of the genotoxic compounds present in the environmental samples will be used as positive controls for the environmentally exposed population. Samples from rural areas will be used as negative controls. The measurement of DNA and protein adducts in these samples will be primarily devoted to those from (a) low molecular weight alkylating agents, (b) compounds that cause oxidative DNA damage and (c) the more complex constituents of urban pollution (e.g. aromatic hydrocarbons). A more preliminary study is planned on populations exposed to pesticides/herbicides. The genotoxic mechanism of these is not as well understood and the assessment of genetic damage will be made only by cytogenetic and mutation assays. It is intended that the project, which is a truly multidisciplinary and multinational effort, should allow (a) a thorough interlaboratory comparison of the application of different biomonitoring procedures for genotoxic exposure, (b) assessment of the relationship between the internal dose of the genotoxic agent (determined from adduct levels) and the subsequent genetic damage associated with the exposure (measured by mutation and cytogenetic effects), (c) determination of the additional genetic burden carried by the exposed populations, (d) study of interindividual variation amongst the subjects in a population, (e) development of novel, more sensitive, specific, and practical methods for biomonitoring such exposures. The ultimate intention of our project will be the optimisation and standardisation of techniques, for general use throughout the Community, for determining genetic risk on an individual person basis. The widespread application of such techniques should have a major impact in efforts to reduce human cancer incidence. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationnatural 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 Topic(s) 01 - Participation in global change programmes Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator MEDICAL RESEARCH COUNCIL EU contribution No data Address Lancaster Road University of Leicester Hodgkin Bui LE1 9HN Leicester United Kingdom See on map Total cost No data Participants (12) Sort alphabetically Sort by EU Contribution Expand all Collapse all Centre International de Recherche sur le Cancer France EU contribution No data Address 150 cours Albert Thomas 69372 Lyon See on map Total cost No data Christie Hospital NHS Trust United Kingdom EU contribution No data Address Wilmslow Road Didsbury M20 9BX Manchester See on map Total cost No data Istituto Nazionale per la Ricerca sul Cancro Italy EU contribution No data Address Viale Benedetto XV 10 16132 Genova See on map Total cost No data MRC Cell Mutation Unit United Kingdom EU contribution No data Address University of Sussex Falmer BN1 9RR Brighton See on map Total cost No data NATIONAL HELLENIC RESEARCH FOUNDATION Greece EU contribution No data Address 48,Vas. Constantinou Avenue 48 11635 ATHENS See on map Total cost No data National Institute of Occupational Health Norway EU contribution No data Address 33 Oslo See on map Total cost No data Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek Netherlands EU contribution No data Address 137-139,Lange Kleiweg 2280 HV Rijswijk See on map Total cost No data Rijksuniversiteit Leiden Netherlands EU contribution No data Address 72,Wassenaarseweg 2300 RA Leiden See on map Total cost No data UNIVERSITY OF AARHUS Denmark EU contribution No data Address 180,Vennelyst Boulevard, 6 8000 AARHUS C See on map Total cost No data UNIVERSITY OF WALES SWANSEA United Kingdom EU contribution No data Address Singleton Park SA2 8PP SWANSEA See on map Total cost No data UNIVERSITY OF YORK United Kingdom EU contribution No data Address Heslington YO10 5YW YORK See on map Total cost No data Vrije Universiteit Brussel Belgium EU contribution No data Address 2,Pleinlaan 1050 Bruxelles See on map Total cost No data