Objective 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. Fields of science natural sciencesbiological sciencesgenetics Programme(s) FP3-ENV 1C - Specific research and technological development programme (EEC) in the field of the environment, 1990-1994 Topic(s) 040204 - Risks to health and the environment from chemical substances Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator Centre International de Recherche sur le Cancer Address 150 cours albert thomas 69372 Lyon France See on map EU contribution No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all Brunel University United Kingdom EU contribution € 0,00 Address UB8 3PH Uxbridge See on map Other funding No data National Institute of Occupational Health Norway EU contribution € 0,00 Address 33 Oslo See on map Other funding No data Rijksuniversiteit Leiden Netherlands EU contribution € 0,00 Address 72,wassenaarseweg 2300 RA Leiden See on map Other funding No data Stiftung Deutsches Krebsforschungszentrum Germany EU contribution € 0,00 Address Im neuenheimer feld 280 69120 Heidelberg See on map Other funding No data
