Objetivo The objective is to harness current techniques in order to identify the most probable, yet hitherto unsuspected, human carcinogens in Europe.In the first part of the study two tasks will be undertaken. First, the hierarchical relationship between DNA damage induced in rodents (comet assay) and mutation induction (lacZ mice) will be consolidated using recently defined tissue-specific genotoxic carcinogens. These carcinogens will be selected to focus the experimental evaluations in rodents on those tissues most often associated with chemically induced carcinogenesis in humans (respiratory tract, skin, bladder). In parallel with these studies, environmental chemicals relevant to the EU will be prioritised by chemical structure, known genetic toxicity and estimated levels of human exposure. This will yield a priority list of 15 chemicals. The first Associated Partner will contribute to the process of prioritisation over the first two years of the study using existing chemical lists/audits. These priority chemicals will be evaluated in rodents using the comet assay to define their primary targets of DNA reactivity. The nine most genotoxic of these compounds will be assessed for mutagenicity to lacZ transgenic mice. Restriction site mutagenesis within the target lacZ gene will also be studied in key affected tissues. Based on these data, a final group of six chemicals will be bioassayed for carcinogenicity over a period of six months using hemisygous p53 mice. P53 genes derived from selected tumours will be sequenced to determine the origin of their loss of function. Independent of these analyses, all bioassay tissues will be conserved for possible future use. If the study succeeds in its aims, six presumptive human carcinogens will be identified for confirmation in subsequent human studies. Should the study fail, a re-appraisal of current approaches to the prediction of possible human carcinogens will be required. Ámbito científico natural sciencesbiological sciencesgeneticsDNAnatural sciencesphysical sciencesastronomyplanetary sciencescometsnatural sciencesbiological sciencesgeneticsmutationnatural sciencesearth and related environmental sciencesenvironmental sciencespollution Programa(s) FP4-ENV 2C - Specific programme of research and technological development in the field of environment and climate, 1994-1998 Tema(s) 02020101 - Risks to human health Convocatoria de propuestas Data not available Régimen de financiación CSC - Cost-sharing contracts Coordinador GERMAN CANCER RESEARCH CENTER Aportación de la UE Sin datos Dirección Im Neuenheimer Feld 280 69120 HEIDELBERG Alemania Ver en el mapa Coste total Sin datos Participantes (4) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo European Communities - Commission of the European Communities - Joint Research centre Italia Aportación de la UE Sin datos Dirección Via E. Fermi 1 21020 Ispra Ver en el mapa Coste total Sin datos Rhône Poulenc Rorer Recherche et Développement Francia Aportación de la UE Sin datos Dirección 13,Quai Jules Guesde 94403 Vitry-sur-Siene Ver en el mapa Coste total Sin datos UNIVERSITY OF WALES SWANSEA Reino Unido Aportación de la UE Sin datos Dirección Singleton Park SA2 8PP SWANSEA Ver en el mapa Coste total Sin datos Zeneca Group plc Reino Unido Aportación de la UE Sin datos Dirección 9 Alderley Park SK10 4TJ Macclesfield Ver en el mapa Coste total Sin datos
