Objective To evaluate the strengths and weaknesses of two available transgenic rodent mutation assays.The importance of determining chemically-induced DNA damage and induced mutations in experimental species is well-established. The currently available rodent assays are empirical and do not provide data on the heritability of induced DNA changes. Two commercially available mutation assays utilising the bacterial lac I/Z gene may present a solution to these problems. The two assay systems are the lac Z construct (Mutamouse, Hazelton) and the lac I construct (Big Blue, Stratagene). Both assay systems are currently being refined and the protocols simplified. Close cooperation with Hazelton and Stratagene will ensure that advances in assay protocols will be incorporated into the project as they occur. The main questions to be addressed are:i) What is the sensitivity and specificity of these assays in respect to carcinogenicity bioassays and established genotoxicity assays, and to what extent is sensitivity chemical and/or tissue specific?ii) To what extent does the cell type selected from a tissue influence the mutation frequency measured?iii) Are these assay most usefully employed as acute mutation assays or as models of the process of rodent carcinogenesis at bioassay dose-levels?iv) What is the relationship between somatic and germ cell mutational effects ?These studies should enable discernment of the appropriate role in human carcinogenic/mutagenic hazard assessment of the lac I/Z rodent mutation assays. Coordination with studies using the non-transgenic restriction site mutation assays (RSM) will be ensured. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesgeneticsmutationsocial sciencessociologygovernancecrisis management 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 Zeneca Group plc Address 9 alderley park SK10 4TJ Macclesfield United Kingdom See on map EU contribution € 0,00 Participants (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all GERMAN CANCER RESEARCH CENTER Germany EU contribution € 0,00 Address Im neuenheimer feld 280 69120 Heidelberg See on map GSF-RESEARCH CENTER FOR ENVIRONMENT AND HEALTH Germany EU contribution € 0,00 Address Ingolstaedter landstrasse 1 85764 Neuherberg See on map
