Objective
ELABORATION AND COMPARATIVE EVALUATION OF TEST SYSTEMS FOR THE ASSESSMENT OF GENETIC EFFECTS OF ENVIRONMENTAL CHEMICALS AND OF THE PRODUCTS OF THEIR METABOLIC TRANSFORMATION.
THE CONTRACT COVERS THREE PROJECTS:
1) IMPROVEMENT OF INCORPORATION OF MAMMALIAN METABOLISM IN IN VITRO TEST SYSTEMS FOR MUTAGENIC ACTIVITY WITH MAMMALIAN CELLS.
IN THIS RESEARCH CELLS OF DIFFERENT ORIGIN WILL BE USED WHICH POSSESS INDOGENOUS METABOLIC CAPACITIES. IN THE FIRST PLACE RAT HEPATOMA CELLS (H35) ARE STUDIED FOR THE INDUCTION OF SCE'S BY GENOTOXIC CHEMICALS, WHICH HAVE MAINTAINED TO A LARGE EXTENT THE CAPABILITIES OF NORMAL RAT LIVER CELLS TO METABOLISE XENOBIOTICS.
2) MOLECULAR DOSIMETRY OG GENOTOXIC DAMAGE OF CHEMICALS IN HUMAN BLOOD CELLS
NUCLEATED CELLS WILL BE USED, WITH SPECIAL ATTENTION TO LYMPHOCYTES AND MONOCYTES.
LYMPHOCYTES WILL BE USED FOR THE DETECTION OF DNA DAMAGE BROUGHT ABOUT BY DIRECTLY ACTING GENOTOXIC CHEMICALS. HOWEVER, WHEN ESPOSITION OCCURS IN VIVO. THESE CELLS CIRCULATE WITH THE BLOOD THROUGH LIVER AND OTHER ORGANS WHERE BIO-ACTIVATION MAY TAKE PLACE AND COMPOUNDS REQUIRING BIO-ACTIVATION MAY ALSO BE DETECTED. WITH MONOCYTES INDIRECTLY ACTING SUBSTANCES MAY BE DETECTED BOTH IN VITRO AND IN VIVO.
IN THE INITIAL PHASE OF THE INVESTIGATIONS HUMAN BLOOD WILL BE EXPOSED IN VITRO TO INDIRECTLY ACTING CHEMICALS USED IN THE COMPARATIVE STUDY OF THE EEC. VARIOUS TECHNIQUES WILL BE USED (E.G. MEASUREMENT OF BREAKS, MEASUREMENT OF ALKALI LABILE SITES AND DNA REPAIR SYNTHESIS). HOWEVER, THE ULTIMATE GOAL THE PROJECT IS TO SET UP IMMUNOLOGICAL TECHNIQUES FOR THE QUANTITATIVE DETECTION OF IDENTIFIED DNA LESIONS IN BLOOD CELLS (MOLECULAR DOSIMETRY).
3) QUANTITATIVE COMPARISON OF GENETIC EFFECTS OF ALKYLATING AGENTS ON THE BASIS OF MOLECULAR DOSIMETRY
IN THIS PART OF THE PROJECT THE RELATION BETWEEN DNA LESIONS AND GENETIC EFFECTS IN DIFFERENT TEST SYSTEMS WILL BE STUDIED UNDER STRICTLY CONTROLLED CONDITIONS WITH A SERIES OF ETHYLATING AGENTS WITH DIFFERENT CHEMICALS REACTIVITY.
THE DETECTION OF IDENTIFIED, ETHYLATION LESIONS WILL BE DONE BY IMPROVED CONVENTIONAL METHODS FOR STUDING DNA LESIONS AND THEIR REPAIR, BUT THE MAIN CONTRIBUTION WILL COME FROM IMMUNOLOGICAL TECHNIQUES, I.P. USING MONOCLONAL ANTIBODIES.
Topic(s)
Data not availableCall for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
2628 XE DELFT
Netherlands