Obiettivo The overall objective of this project is to develop assay systems to detect genotoxic and non-genotoxic carcinogens based on an improved molecular and cellular understanding of human cell transformation mechanisms.The specific aims are to (i) compare the molecular mechanisms of cell immortalization, a rate-limiting step in cell transformation, of human and rodent cells, (ii) examine whether induction of genomic instability is an important step in human cell transformation, (iii) develop biological markers useful for identifying transformed epithelial cells of various stages of transformation, and (iv) examine the usefulness of established human epithelial cell lines to detect carcinogens involved at different stages of carcinogenesis.The project is aimed at establishing reliable cell transformation systems which detect human carcinogens acting by different mechanisms. We plan :a) To investigate the differences between human and rodent cells in resistance to transformation with emphasis on : (i) Induction of immortalization. (ii) Induction of genomic instability.b) To identify those transformation phenotypes of human epithelial cells which can be induced by carcinogens and to identify biological markers for these responses, which can be used as markers for different stages of transformation of human epithelial cells.c) To develop epithelial cell transformation systems based on the results from 1 and 2. The intrinsic resistance of human cells to transformation means that it is unlikely to be possible to generate a system in which the full transformation of normal human epithelial cells can be reproducibly achieved and quantified. Therefore, we plan to establish separate systems for studying each of the individual steps in the process which respond to non-genotoxic carcinogens (i.e. manipulated human epithelial cell systems requiring only single events to progress to a further transformation stage).d) To conduct a validation of assay systems with selected carcinogens, genotoxic and non-genotoxic. Campo scientifico natural sciencesbiological sciencesgenetics Programma(i) FP3-ENV 1C - Specific research and technological development programme (EEC) in the field of the environment, 1990-1994 Argomento(i) 040204 - Risks to health and the environment from chemical substances Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore Centre International de Recherche sur le Cancer Contributo UE Nessun dato Indirizzo 150 cours Albert Thomas 69372 Lyon Francia Mostra sulla mappa Costo totale Nessun dato Partecipanti (4) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto Brunel University Regno Unito Contributo UE Nessun dato Indirizzo UB8 3PH Uxbridge Mostra sulla mappa Costo totale Nessun dato National Institute of Occupational Health Norvegia Contributo UE Nessun dato Indirizzo 33 Oslo Mostra sulla mappa Costo totale Nessun dato Rijksuniversiteit Leiden Paesi Bassi Contributo UE Nessun dato Indirizzo 72,Wassenaarseweg 2300 RA Leiden Mostra sulla mappa Costo totale Nessun dato Stiftung Deutsches Krebsforschungszentrum Germania Contributo UE Nessun dato Indirizzo Im Neuenheimer Feld 280 69120 Heidelberg Mostra sulla mappa Costo totale Nessun dato
